Pharmacology Biochemistry and Behavior最新文献_第8页

Administration of paroxetine during pregnancy affects behavioral changes and hippocampal cell proliferation in male offspring in rats 妊娠期给予帕罗西汀影响雄性后代大鼠行为改变和海马细胞增殖

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-05-26 DOI: 10.1016/j.pbb.2025.174041

Junko Horie , Tomoya Kinjo , Masanobu Ito , Toshihito Suzuki

Background

Although the use of antidepressants during pregnancy has increased over the last several decades, their safety has remained a topic of debate. Selective serotonin reuptake inhibitors (SSRIs) can cross the placenta and affect perinatal outcomes in infants exposed during pregnancy. Recent studies suggest new risks for not only for structural malformations, but also long-term behavioral, developmental, and emotional disorders in offspring.

Aim

We aimed to elucidate the effects by which in utero paroxetine exposure may affect the behavior and hippocampus of the offspring of paroxetine-treated rodent mothers.

Methods

Paroxetine was administered daily to pregnant female Wistar rats from embryonic day (ED) 12.5 to ED 21 with oral sondes. Paroxetine 1 mg/kg/day or paroxetine 2.5 mg/kg/day or saline was given to the control group. We evaluated spontaneous locomotor activity, spontaneous alternation behavior using the Y-maze test, and anxiety behavior using the elevated plus maze (EPM) in male offspring at postnatal day 30. Bromodeoxyuridine (BrdU)-positive cells in the hippocampus were counted using a fluorescence microscope.

Results

Locomotor activities significantly increased in the paroxetine 2.5 mg compared with the control group. The paroxetine 2.5 mg group spent less time in the closed arm than did the control and paroxetine 1 mg groups in the EPM. The number of BrdU-positive cells in the dentate gyrus was significantly increased in the paroxetine 2.5 mg compared with the control group.

Conclusions

These findings suggest that oral administration of paroxetine during pregnancy induces hyperactivity, decreases anxiety, and increases cell proliferation in the hippocampus of male offspring.

虽然在过去的几十年里，怀孕期间使用抗抑郁药的情况有所增加，但它们的安全性仍然是一个有争议的话题。选择性5 -羟色胺再摄取抑制剂（SSRIs）可以穿过胎盘并影响怀孕期间暴露的婴儿围产期结局。最近的研究表明，新的风险不仅是结构畸形，而且还包括后代的长期行为、发育和情绪障碍。目的：我们旨在阐明子宫内暴露于帕罗西汀可能影响帕罗西汀治疗的啮齿动物母亲后代的行为和海马的影响。方法妊娠雌性Wistar大鼠从胚胎期12.5 ~ 21天每天口服帕罗西汀。对照组给予帕罗西汀1 mg/kg/day或帕罗西汀2.5 mg/kg/day或生理盐水。在出生后第30天，我们用y迷宫测试评估了雄性后代的自发运动活动、自发交替行为，用升高正迷宫（EPM）评估了焦虑行为。荧光显微镜下计数海马中溴脱氧尿苷（BrdU）阳性细胞。结果与对照组相比，帕罗西汀2.5 mg组心肌运动活性明显增强。与对照组和帕罗西汀1 mg组相比，帕罗西汀2.5 mg组在EPM中的封闭臂时间更短。与对照组相比，paroxetine 2.5 mg组齿状回brdu阳性细胞数量明显增加。结论妊娠期口服帕罗西汀可诱导雄性后代多动、减轻焦虑、增加海马细胞增殖。

{"title":"Administration of paroxetine during pregnancy affects behavioral changes and hippocampal cell proliferation in male offspring in rats","authors":"Junko Horie , Tomoya Kinjo , Masanobu Ito , Toshihito Suzuki","doi":"10.1016/j.pbb.2025.174041","DOIUrl":"10.1016/j.pbb.2025.174041","url":null,"abstract":"<div><h3>Background</h3><div>Although the use of antidepressants during pregnancy has increased over the last several decades, their safety has remained a topic of debate. Selective serotonin reuptake inhibitors (SSRIs) can cross the placenta and affect perinatal outcomes in infants exposed during pregnancy. Recent studies suggest new risks for not only for structural malformations, but also long-term behavioral, developmental, and emotional disorders in offspring.</div></div><div><h3>Aim</h3><div>We aimed to elucidate the effects by which in utero paroxetine exposure may affect the behavior and hippocampus of the offspring of paroxetine-treated rodent mothers.</div></div><div><h3>Methods</h3><div>Paroxetine was administered daily to pregnant female Wistar rats from embryonic day (ED) 12.5 to ED 21 with oral sondes. Paroxetine 1 mg/kg/day or paroxetine 2.5 mg/kg/day or saline was given to the control group. We evaluated spontaneous locomotor activity, spontaneous alternation behavior using the Y-maze test, and anxiety behavior using the elevated plus maze (EPM) in male offspring at postnatal day 30. Bromodeoxyuridine (BrdU)-positive cells in the hippocampus were counted using a fluorescence microscope.</div></div><div><h3>Results</h3><div>Locomotor activities significantly increased in the paroxetine 2.5 mg compared with the control group. The paroxetine 2.5 mg group spent less time in the closed arm than did the control and paroxetine 1 mg groups in the EPM. The number of BrdU-positive cells in the dentate gyrus was significantly increased in the paroxetine 2.5 mg compared with the control group.</div></div><div><h3>Conclusions</h3><div>These findings suggest that oral administration of paroxetine during pregnancy induces hyperactivity, decreases anxiety, and increases cell proliferation in the hippocampus of male offspring.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"253 ","pages":"Article 174041"},"PeriodicalIF":3.3,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144168606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Enhanced novelty-seeking after early adolescent exposure to vicarious social defeat predicts the vulnerability of female mice to cocaine reward 在青春期早期暴露于替代性的社会失败后，寻求新奇事物的增强预示着雌性老鼠对可卡因奖励的脆弱性。

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-05-23 DOI: 10.1016/j.pbb.2025.174039

María Ángeles Martínez-Caballero , Claudia Calpe-López , María Pilar García-Pardo , María Carmen Arenas , Jose Enrique de la Rubia Ortí , María Benlloch , Carmen Manzanedo , María Asunción Aguilar

Stressful experiences can have a serious impact on adolescents, as the process of brain maturation, particularly of the prefrontal cortex, takes place during this developmental period. In animal models, male mice exposed to social defeat during early or late adolescence show increased vulnerability to cocaine reward, but this effect has only been studied in late adolescent female mice exposed to Vicarious Intermittent Social Defeat (VISD). The aim of the present study was to investigate the biochemical and behavioural effects of exposure to VISD during early adolescence in female mice. VISD only induced anxiety-like symptoms in the elevated plus maze (EPM) and increased novelty-seeking behaviour in the hole-board test. Furthermore, the behavioural profile of VISD-exposed mice in these tests was associated with their vulnerability or resilience to cocaine reward in adulthood. Female mice that exhibited a higher frequency of entries in the closed arms of the EPM and a lower latency of dips in the hole-board subsequently acquired cocaine-induced conditioned place preference. Thus, exposure of female mice to VISD during early adolescence also induced short-term changes that increased sensitivity to cocaine reward in susceptible individuals.

压力经历会对青少年产生严重影响，因为大脑成熟的过程，特别是前额皮质，发生在这个发育时期。在动物模型中，在青春期早期或晚期暴露于社交失败的雄性小鼠对可卡因奖励的脆弱性增加，但这种影响仅在青春期晚期暴露于替代性间歇性社交失败（VISD）的雌性小鼠中进行了研究。本研究的目的是研究雌性小鼠青春期早期暴露于VISD的生化和行为影响。VISD仅在升高+迷宫（EPM）中引起焦虑样症状，并在孔板测试中增加寻求新奇的行为。此外，在这些测试中，暴露于visd的小鼠的行为特征与它们成年后对可卡因奖励的脆弱性或恢复力有关。雌性小鼠进入EPM闭合臂的频率较高，在孔板上的潜伏期较低，随后获得了可卡因诱导的条件位置偏好。因此，雌性小鼠在青春期早期暴露于VISD也会引起短期变化，增加易感个体对可卡因奖励的敏感性。

{"title":"Enhanced novelty-seeking after early adolescent exposure to vicarious social defeat predicts the vulnerability of female mice to cocaine reward","authors":"María Ángeles Martínez-Caballero , Claudia Calpe-López , María Pilar García-Pardo , María Carmen Arenas , Jose Enrique de la Rubia Ortí , María Benlloch , Carmen Manzanedo , María Asunción Aguilar","doi":"10.1016/j.pbb.2025.174039","DOIUrl":"10.1016/j.pbb.2025.174039","url":null,"abstract":"<div><div>Stressful experiences can have a serious impact on adolescents, as the process of brain maturation, particularly of the prefrontal cortex, takes place during this developmental period. In animal models, male mice exposed to social defeat during early or late adolescence show increased vulnerability to cocaine reward, but this effect has only been studied in late adolescent female mice exposed to Vicarious Intermittent Social Defeat (VISD). The aim of the present study was to investigate the biochemical and behavioural effects of exposure to VISD during early adolescence in female mice. VISD only induced anxiety-like symptoms in the elevated plus maze (EPM) and increased novelty-seeking behaviour in the hole-board test. Furthermore, the behavioural profile of VISD-exposed mice in these tests was associated with their vulnerability or resilience to cocaine reward in adulthood. Female mice that exhibited a higher frequency of entries in the closed arms of the EPM and a lower latency of dips in the hole-board subsequently acquired cocaine-induced conditioned place preference. Thus, exposure of female mice to VISD during early adolescence also induced short-term changes that increased sensitivity to cocaine reward in susceptible individuals.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"253 ","pages":"Article 174039"},"PeriodicalIF":3.3,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pharmacological and genetic manipulation of glyoxalase-1 (GLO1) does not alter locomotor responses or conditioned place preference induced by cocaine or oxycodone. 乙二醛酶-1 （GLO1）的药理学和遗传学操作不会改变可卡因或羟考酮诱导的运动反应或条件位置偏好。

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-05-22 DOI: 10.1016/j.pbb.2025.174040

Elizabeth Alcantara , Michelle R. Doyle , Clara A. Ortez , Anne Ilustrisimo , Bloom Stromberg , Amanda M. Barkley-Levenson , Abraham A. Palmer

Methylglyoxal (MG) is an endogenously produced non-enzymatic side product of glycolysis that acts as a partial agonist at GABA_A receptors. MG is metabolized by the enzyme glyoxalase-1 (GLO1). Inhibition of GLO1 increases methylglyoxal levels, and has been shown to modulate various behaviors, including decreasing seeking of cocaine-paired cues and ethanol consumption. The goal of these studies was to determine whether manipulation of GLO1 could alter cocaine- or oxycodone-induced locomotor activation and/or conditioned place preference (CPP) to cocaine or oxycodone. We used both pharmacological and genetic manipulations of GLO1 to address this question. Administration of the GLO1 inhibitor s-bromobenzylglutathione cyclopentyl diester (pBBG) did not alter the locomotor response to cocaine or oxycodone. Additionally, pBBG had no significant effect on place preference for cocaine or oxycodone. Genetic knockdown of Glo1, which is conceptually similar to pharmacological inhibition, did not have any significant effects on CPP to cocaine. Finally, Glo1 overexpression did not affect locomotor response to cocaine. In summary, our results did not show any effect of pharmacological or genetic manipulations of GLO1 on the locomotor response or CPP to either cocaine or oxycodone.

甲基乙二醛（MG）是糖酵解的内源性非酶副产物，作为GABAA受体的部分激动剂。MG由乙二醛酶-1 （GLO1）代谢。抑制GLO1增加甲基乙二醛水平，并已被证明可以调节多种行为，包括减少寻求可卡因配对线索和乙醇消耗。这些研究的目的是确定GLO1的操纵是否可以改变可卡因或羟考酮诱导的运动激活和/或对可卡因或羟考酮的条件性位置偏好（CPP）。我们使用GLO1的药理学和遗传学操作来解决这个问题。GLO1抑制剂s-溴苄基谷胱甘肽环戊二酯（pBBG）的使用没有改变对可卡因或羟考酮的运动反应。此外，pBBG对可卡因或羟考酮的位置偏好没有显著影响。基因敲除Glo1在概念上类似于药物抑制，对可卡因的CPP没有任何显著影响。最后，Glo1过表达不影响对可卡因的运动反应。总之，我们的结果没有显示GLO1的药理学或遗传操作对可卡因或羟考酮的运动反应或CPP有任何影响。

{"title":"Pharmacological and genetic manipulation of glyoxalase-1 (GLO1) does not alter locomotor responses or conditioned place preference induced by cocaine or oxycodone.","authors":"Elizabeth Alcantara , Michelle R. Doyle , Clara A. Ortez , Anne Ilustrisimo , Bloom Stromberg , Amanda M. Barkley-Levenson , Abraham A. Palmer","doi":"10.1016/j.pbb.2025.174040","DOIUrl":"10.1016/j.pbb.2025.174040","url":null,"abstract":"<div><div>Methylglyoxal (MG) is an endogenously produced non-enzymatic side product of glycolysis that acts as a partial agonist at GABA<sub>A</sub> receptors. MG is metabolized by the enzyme glyoxalase-1 (GLO1). Inhibition of GLO1 increases methylglyoxal levels, and has been shown to modulate various behaviors, including decreasing seeking of cocaine-paired cues and ethanol consumption. The goal of these studies was to determine whether manipulation of GLO1 could alter cocaine- or oxycodone-induced locomotor activation and/or conditioned place preference (CPP) to cocaine or oxycodone. We used both pharmacological and genetic manipulations of GLO1 to address this question. Administration of the GLO1 inhibitor s-bromobenzylglutathione cyclopentyl diester (pBBG) did not alter the locomotor response to cocaine or oxycodone. Additionally, pBBG had no significant effect on place preference for cocaine or oxycodone. Genetic knockdown of <em>Glo1</em>, which is conceptually similar to pharmacological inhibition, did not have any significant effects on CPP to cocaine. Finally, <em>Glo1</em> overexpression did not affect locomotor response to cocaine. In summary, our results did not show any effect of pharmacological or genetic manipulations of GLO1 on the locomotor response or CPP to either cocaine or oxycodone.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"253 ","pages":"Article 174040"},"PeriodicalIF":3.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144124569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sex-dependent changes induced by combined low-level systemic inflammation and chronic mild unpredictable stress in rats are partially attenuated by positive modulation of α5 GABAA receptors 大鼠低水平全身炎症和慢性轻度不可预测应激联合引起的性别依赖性变化可通过α5 GABAA受体的阳性调节部分减弱

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-05-14 DOI: 10.1016/j.pbb.2025.174032

Jana Ivanović , Jovana Aranđelović , Kristina Jezdić , Branka Divović Matović , Ivan Jančić , Bojan Batinić , Dishary Sharmin , Prithu Mondal , James M. Cook , Miroslav M. Savić

The response to prolonged mild stress is dichotomous, has been associated with depression, anxiety and cognitive impairment, and may be modulated by various factors such as sex or GABA-ergic transmission. We investigated in rats the sex-dependent effects of four doses of lipopolysaccharide (LPS) in one week, followed by four weeks of chronic unpredictable mild stress (CUMS), on behavioral parameters assessed in the weekly sucrose preference test and spontaneous locomotor activity, as well as in the behavioral battery (elevated-plus-maze test, resident-intruder test, three-chamber test and forced-swim test) conducted after 7 days of treatment with GL-II-73, a positive allosteric modulator selective for α5 GABA_A receptors (LPS/CUMS-GL-II-73), or with solvent (LPS/CUMS-SOL), beginning after the third week of CUMS. At the end of stress, sucrose intake was significantly increased in LPS/CUMS-SOL compared to male controls (CRTL); in females, LPS/CUMS-GL-II-73 showed a significantly higher preference for sucrose than CTRL-SOL. In males, forced swimming time was significantly longer in LPS/CUMS-SOL compared to CTRL-SOL. Social play in the resident-intruder test was reduced in female LPS/CUMS-SOL, and GL-II-73 and GL-II-73 tended to reversed this stress effect. LPS/CUMS-GL-II-73 males showed no significant social recognition in the three-chamber test. Ex vivo tests showed an increase in Gabra5 gene expression in the ventral hippocampus in LPS/CUMS-GL-II-73 compared to CTRL-SOL. The subtle changes in the measured parameters suggest that the clinical benefit of positive modulation of α5 GABA_A receptors may result from focusing on the sex-specific niches of behavioral domains affected by prolonged stressors.

对长期轻度压力的反应是两面性的，与抑郁、焦虑和认知障碍有关，并可能受到各种因素的调节，如性别或氨基丁酸能传递。我们研究了四种剂量的脂多糖（LPS）在一周内对大鼠的性别依赖性影响，随后是4周的慢性不可预测轻度应激（CUMS），对每周蔗糖偏好测试和自发运动活动中评估的行为参数，以及在用GL-II-73治疗7天后进行的行为电池（升高加迷宫测试、居住者测试、三室测试和强迫游泳测试）的影响。一种选择性α5 GABAA受体（LPS/ cms - gl - ii -73）或与溶剂（LPS/ cms - sol）的正变质调节剂，在CUMS治疗第三周后开始。应激结束时，LPS/ coms - sol组的蔗糖摄入量显著高于雄性对照组（CRTL）；在雌性中，LPS/ cams - gl - ii -73对蔗糖的偏好明显高于CTRL-SOL。在男性中，LPS/CUMS-SOL组的强迫游泳时间明显长于CTRL-SOL组。雌性LPS/ cms - sol的社会玩耍减少，而GL-II-73和GL-II-73倾向于逆转这种应激效应。LPS/ cms - gl - ii -73雄性在三室测试中没有明显的社会认知。体外实验显示，与CTRL-SOL相比，LPS/ cms - gl - ii -73小鼠腹侧海马Gabra5基因表达增加。测量参数的微妙变化表明，α5 GABAA受体的阳性调节可能是由于关注受长时间应激影响的行为域的性别特异性壁龛而产生的临床益处。

{"title":"Sex-dependent changes induced by combined low-level systemic inflammation and chronic mild unpredictable stress in rats are partially attenuated by positive modulation of α5 GABAA receptors","authors":"Jana Ivanović , Jovana Aranđelović , Kristina Jezdić , Branka Divović Matović , Ivan Jančić , Bojan Batinić , Dishary Sharmin , Prithu Mondal , James M. Cook , Miroslav M. Savić","doi":"10.1016/j.pbb.2025.174032","DOIUrl":"10.1016/j.pbb.2025.174032","url":null,"abstract":"<div><div>The response to prolonged mild stress is dichotomous, has been associated with depression, anxiety and cognitive impairment, and may be modulated by various factors such as sex or GABA-ergic transmission. We investigated in rats the sex-dependent effects of four doses of lipopolysaccharide (LPS) in one week, followed by four weeks of chronic unpredictable mild stress (CUMS), on behavioral parameters assessed in the weekly sucrose preference test and spontaneous locomotor activity, as well as in the behavioral battery (elevated-plus-maze test, resident-intruder test, three-chamber test and forced-swim test) conducted after 7 days of treatment with GL-II-73, a positive allosteric modulator selective for α5 GABA<sub>A</sub> receptors (LPS/CUMS-GL-II-73), or with solvent (LPS/CUMS-SOL), beginning after the third week of CUMS. At the end of stress, sucrose intake was significantly increased in LPS/CUMS-SOL compared to male controls (CRTL); in females, LPS/CUMS-GL-II-73 showed a significantly higher preference for sucrose than CTRL-SOL. In males, forced swimming time was significantly longer in LPS/CUMS-SOL compared to CTRL-SOL. Social play in the resident-intruder test was reduced in female LPS/CUMS-SOL, and GL-II-73 and GL-II-73 tended to reversed this stress effect. LPS/CUMS-GL-II-73 males showed no significant social recognition in the three-chamber test. Ex vivo tests showed an increase in <em>Gabra5</em> gene expression in the ventral hippocampus in LPS/CUMS-GL-II-73 compared to CTRL-SOL. The subtle changes in the measured parameters suggest that the clinical benefit of positive modulation of α5 GABA<sub>A</sub> receptors may result from focusing on the sex-specific niches of behavioral domains affected by prolonged stressors.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"253 ","pages":"Article 174032"},"PeriodicalIF":3.3,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144068453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Reward contamination in restrictive anorexia nervosa: A meta-analysis of functional MRI studies 限制性神经性厌食症的奖励污染：功能性MRI研究的荟萃分析

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-05-08 DOI: 10.1016/j.pbb.2025.174031

Charlotte S. Rye , Felippe E. Amorim , Laetitia H.E. Ward , Amy L. Milton

Individuals with anorexia nervosa (AN) are typically anhedonic, leading to the suggestion that intrinsic disturbances of reward processing may represent a trait marker of the disorder. Previous studies have used task-based functional magnetic resonance imaging (fMRI) to investigate reward-related brain activity in AN and reported altered activation in the prefrontal cortex, dorsal posterior cingulate cortex, and rostral anterior cingulate cortex. However, likely due to the varied paradigms and methodologies used, as well as the heterogeneity in sample characteristics, results have proved inconsistent. To determine whether AN patients with the restrictive subtype (AN-r) show different reward-induced activation patterns to matched healthy controls (HCs) at different illness stages, we conducted a meta-analysis of 19 task-based fMRI studies of reward-processing. Using the seed-based differential mapping (SDM) technique, we found differences in reward-related brain activity between AN-r and HCs. Moreover, different brain regions showed differential activation across illness stages, with the direction and magnitude of effects dependent on specific task stimuli. These findings suggest that those with AN-r show distorted reward processing as a consequence of reward contamination and alterations in valence assignment to reward stimuli. In weight-recovered AN-r patients, differences to HCs persisted but were limited to regions known to exhibit significant atrophy in AN-r, indicating that altered reward processing is associated with anorectic undernutrition. These findings have implications for developing pharmacological treatments to aid psychological recovery in AN-r.

神经性厌食症（AN）的个体是典型的快乐缺乏症，导致奖励处理的内在干扰可能是该疾病的特征标记。先前的研究使用基于任务的功能性磁共振成像（fMRI）来研究AN中与奖励相关的大脑活动，并报道了前额叶皮层、后扣带皮层背侧和前扣带皮层吻侧的激活改变。然而，可能由于所使用的范式和方法的不同，以及样本特征的异质性，结果被证明是不一致的。为了确定AN限制性亚型（AN-r）患者在不同疾病阶段是否表现出与匹配健康对照（hc）不同的奖励诱导激活模式，我们对19项基于任务的fMRI奖励处理研究进行了荟萃分析。使用基于种子的差分映射（SDM）技术，我们发现AN-r和hc之间奖赏相关的大脑活动存在差异。此外，不同的大脑区域在不同的疾病阶段表现出不同的激活，其作用的方向和大小取决于特定的任务刺激。这些发现表明，AN-r患者表现出扭曲的奖励加工，这是奖励污染和对奖励刺激的效价分配改变的结果。在体重恢复的AN-r患者中，hcc的差异持续存在，但仅限于已知AN-r显着萎缩的区域，这表明奖赏加工的改变与厌食性营养不良有关。这些发现对开发药物治疗来帮助AN-r患者的心理恢复具有启示意义。

{"title":"Reward contamination in restrictive anorexia nervosa: A meta-analysis of functional MRI studies","authors":"Charlotte S. Rye , Felippe E. Amorim , Laetitia H.E. Ward , Amy L. Milton","doi":"10.1016/j.pbb.2025.174031","DOIUrl":"10.1016/j.pbb.2025.174031","url":null,"abstract":"<div><div>Individuals with anorexia nervosa (AN) are typically anhedonic, leading to the suggestion that intrinsic disturbances of reward processing may represent a trait marker of the disorder. Previous studies have used task-based functional magnetic resonance imaging (fMRI) to investigate reward-related brain activity in AN and reported altered activation in the prefrontal cortex, dorsal posterior cingulate cortex, and rostral anterior cingulate cortex. However, likely due to the varied paradigms and methodologies used, as well as the heterogeneity in sample characteristics, results have proved inconsistent. To determine whether AN patients with the restrictive subtype (AN-r) show different reward-induced activation patterns to matched healthy controls (HCs) at different illness stages, we conducted a meta-analysis of 19 task-based fMRI studies of reward-processing. Using the seed-based differential mapping (SDM) technique, we found differences in reward-related brain activity between AN-r and HCs. Moreover, different brain regions showed differential activation across illness stages, with the direction and magnitude of effects dependent on specific task stimuli. These findings suggest that those with AN-r show distorted reward processing as a consequence of reward contamination and alterations in valence assignment to reward stimuli. In weight-recovered AN-r patients, differences to HCs persisted but were limited to regions known to exhibit significant atrophy in AN-r, indicating that altered reward processing is associated with anorectic undernutrition. These findings have implications for developing pharmacological treatments to aid psychological recovery in AN-r.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"252 ","pages":"Article 174031"},"PeriodicalIF":3.3,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143928044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Postnatal propionic acid exposure disrupts hippocampal agmatine homeostasis leading to social deficits and cognitive impairment in autism spectrum disorder-like phenotype in rats 产后丙酸暴露破坏大鼠海马agmatine稳态，导致自闭症谱系障碍样表型的社会缺陷和认知障碍

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-05-01 DOI: 10.1016/j.pbb.2025.174030

Manasi Tadas , Nitu Wankhede , Pranali Chandurkar , Nandkishor Kotagale , Milind Umekar , Raj Katariya , Akash Waghade , Dadasaheb Kokare , Brijesh Taksande

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by a range of symptoms including impaired social interaction and cognitive deficits. Although the exact pathogenesis of ASD is not well established, recent clinical findings suggest a decline in levels of biogenic amine agmatine in autistic patients. The present study was designed to investigate the impact of postnatal propionic acid (PPA) exposure on hippocampal agmatine homeostasis in male rat pups and to explore a new therapeutic intervention for ASD using agmatine as a biological target. PPA is commonly used in experimental models of ASD due to its ability to induce social deficits, cognitive impairments, and stereotyped behaviors, which closely resemble key characteristics of ASD. Male rat pups were administered with PPA via the intrahippocampal route bilaterally (25 μg/0.25 μl per side) on PND-21 to simulate the ASD phenotype, and its subsequent effect on the endogenous agmatinergic system. The influence of agmatine treatment and its endogenous modulation on ASD-like phenotypes was also investigated. Behavioral assessments revealed that PPA exposure reduced sociability and social preference, caused learning and memory impairment in the Morris water maze, increased anxiety-like behavior in the elevated plus maze, and reduced exploratory behavior in the hole board test. Neurochemical analyses showed a decrease in agmatine concentration and an increase in its degrading enzyme agmatinase in the hippocampus. PPA treatment altered the content of GABA, glutamate, TNF-α, IL-6, BDNF, and also resulted in increased astrogliosis and neurotoxicity within the hippocampus. Chronic agmatine treatment and its endogenous modulation ameliorated the behavioral and biochemical disruptions induced by PPA exposure. This study highlights the critical role of hippocampal agmatinergic pathway in the etiopathogenesis of ASD, positioning agmatine as a promising therapeutic target for its treatment.

自闭症谱系障碍（ASD）是一种复杂的神经发育疾病，其特征是一系列症状，包括社交障碍和认知缺陷。虽然ASD的确切发病机制尚不清楚，但最近的临床研究结果表明，自闭症患者体内的生物源胺胍水平下降。本研究旨在探讨出生后丙酸（PPA）暴露对雄性大鼠幼鼠海马agmatine稳态的影响，并探索以agmatine为生物学靶点的ASD治疗干预新方法。PPA通常用于ASD的实验模型，因为它能够诱导社会缺陷、认知障碍和刻板行为，这些与ASD的关键特征非常相似。通过PND-21双侧海马内通路给药PPA（每侧25 μg/0.25 μl），模拟ASD表型及其对内源性agmatinergic系统的影响。还研究了胍丁氨酸处理及其内源调控对asd样表型的影响。行为评估显示，PPA暴露降低了社交能力和社会偏好，导致Morris水迷宫的学习和记忆障碍，升高+迷宫的焦虑样行为增加，孔板测试的探索行为减少。神经化学分析显示，海马体内的agmatinase浓度下降，其降解酶agmatinase增加。PPA处理改变了GABA、谷氨酸、TNF-α、IL-6、BDNF的含量，还导致海马内星形胶质细胞增生和神经毒性增加。慢性胍丁氨酸治疗及其内源性调节改善了PPA暴露引起的行为和生化破坏。本研究强调了海马agmatinergine通路在ASD发病机制中的关键作用，将agmatine定位为ASD治疗的有希望的治疗靶点。

{"title":"Postnatal propionic acid exposure disrupts hippocampal agmatine homeostasis leading to social deficits and cognitive impairment in autism spectrum disorder-like phenotype in rats","authors":"Manasi Tadas , Nitu Wankhede , Pranali Chandurkar , Nandkishor Kotagale , Milind Umekar , Raj Katariya , Akash Waghade , Dadasaheb Kokare , Brijesh Taksande","doi":"10.1016/j.pbb.2025.174030","DOIUrl":"10.1016/j.pbb.2025.174030","url":null,"abstract":"<div><div>Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by a range of symptoms including impaired social interaction and cognitive deficits. Although the exact pathogenesis of ASD is not well established, recent clinical findings suggest a decline in levels of biogenic amine agmatine in autistic patients. The present study was designed to investigate the impact of postnatal propionic acid (PPA) exposure on hippocampal agmatine homeostasis in male rat pups and to explore a new therapeutic intervention for ASD using agmatine as a biological target. PPA is commonly used in experimental models of ASD due to its ability to induce social deficits, cognitive impairments, and stereotyped behaviors, which closely resemble key characteristics of ASD. Male rat pups were administered with PPA via the intrahippocampal route bilaterally (25 μg/0.25 μl per side) on PND-21 to simulate the ASD phenotype, and its subsequent effect on the endogenous agmatinergic system. The influence of agmatine treatment and its endogenous modulation on ASD-like phenotypes was also investigated. Behavioral assessments revealed that PPA exposure reduced sociability and social preference, caused learning and memory impairment in the Morris water maze, increased anxiety-like behavior in the elevated plus maze, and reduced exploratory behavior in the hole board test. Neurochemical analyses showed a decrease in agmatine concentration and an increase in its degrading enzyme agmatinase in the hippocampus. PPA treatment altered the content of GABA, glutamate, TNF-α, IL-6, BDNF, and also resulted in increased astrogliosis and neurotoxicity within the hippocampus. Chronic agmatine treatment and its endogenous modulation ameliorated the behavioral and biochemical disruptions induced by PPA exposure. This study highlights the critical role of hippocampal agmatinergic pathway in the etiopathogenesis of ASD, positioning agmatine as a promising therapeutic target for its treatment.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"252 ","pages":"Article 174030"},"PeriodicalIF":3.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143911623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Crisugabalin, a ligand for the α2δ subunit of voltage-gated calcium channels, exhibits no obvious abuse potential in rodents Crisugabalin是电压门控钙通道α2δ亚基的配体，在啮齿类动物中没有明显的滥用潜力

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-05-01 DOI: 10.1016/j.pbb.2025.174015

Xiaoli Gou , Yijiang Liu , Qidi Ye , Lingzhi He , Ying Chen , Yansheng Dong , Qingyuan Meng , Zongjun Shi , Yao Li , Yao Lu , Ju Wang , Linggao Zeng

Crisugabalin, a novel third-generation ligand targeting the α2δ subunit of voltage-gated calcium channels, has been approved in China for the treatment of pain associated with diabetic peripheral neuropathy and postherpetic neuralgia. Existing research suggests that ligands for the α2δ subunit of voltage-gated calcium channels may carry a risk of abuse. To evaluate the abuse potential of crisugabalin, five well-recognized animal models were utilized in these preclinical studies. Firstly, an intravenous self-administration paradigm was implemented in rats that were self-administering propofol to assess the reinforcing effects of crisugabalin. Secondly, a rat drug discrimination study was employed to determine the pharmacological similarity between crisugabalin and the training drug midazolam. Then, a conditioned place preference (CPP) paradigm in rats was utilized to evaluate the rewarding properties of crisugabalin. After that, a spontaneous withdrawal study was conducted in rats chronically treated with crisugabalin to examine the liability of developing physical dependence. Finally, a mouse pentylenetetrazol-induced convulsion model was used following chronic exposure to crisugabalin to assess its potential for physical dependence. The results indicated that crisugabalin showed no positive reinforcing effects and did not display midazolam-like discriminative stimulus effects. Moreover, crisugabalin did not induce significant CPP in rats and there was no risk of physical dependence in the pentylenetetrazol-induced convulsion model. In the rat spontaneous withdrawal study, crisugabalin demonstrated a very low level of physical dependence. These findings suggest that crisugabalin has minimal to no potential for abuse, thereby establishing itself as a safer option relative to pregabalin and mirogabalin.

Crisugabalin是一种新型的第三代配体，靶向电压门控钙通道α2δ亚基，已在中国获批用于治疗糖尿病周围神经病变和带状疱疹后神经痛。现有研究表明，电压门控钙通道α2δ亚基配体可能存在滥用风险。为了评估crisugabalin的滥用潜力，在这些临床前研究中使用了五种公认的动物模型。首先，在自我给药异丙酚的大鼠中实施静脉自我给药范式，以评估crisugabalin的强化作用。其次，采用大鼠药物鉴别研究，确定crisugabalin与训练药物咪达唑仑的药理学相似性。然后，采用大鼠条件位置偏好（CPP）范式评价crisugabalin的奖励特性。在此之后，对长期使用crisugabalin的大鼠进行了自发戒断研究，以检查发生身体依赖的责任。最后，使用慢性暴露于crisugabalin后的小鼠戊四唑诱导惊厥模型来评估其身体依赖的可能性。结果表明，crisugabalin无正向强化作用，不表现出类似咪达唑仑的区别刺激作用。此外，crisugabalin未引起大鼠明显的CPP，并且在戊四唑诱导的惊厥模型中没有身体依赖的风险。在大鼠自发戒断研究中，crisugabalin表现出非常低的身体依赖性。这些发现表明，crisugabalin几乎没有滥用的可能性，因此相对于普瑞巴林和米罗巴林，它是一种更安全的选择。

{"title":"Crisugabalin, a ligand for the α2δ subunit of voltage-gated calcium channels, exhibits no obvious abuse potential in rodents","authors":"Xiaoli Gou , Yijiang Liu , Qidi Ye , Lingzhi He , Ying Chen , Yansheng Dong , Qingyuan Meng , Zongjun Shi , Yao Li , Yao Lu , Ju Wang , Linggao Zeng","doi":"10.1016/j.pbb.2025.174015","DOIUrl":"10.1016/j.pbb.2025.174015","url":null,"abstract":"<div><div>Crisugabalin, a novel third-generation ligand targeting the <em>α2δ</em> subunit of voltage-gated calcium channels, has been approved in China for the treatment of pain associated with diabetic peripheral neuropathy and postherpetic neuralgia. Existing research suggests that ligands for the <em>α2δ</em> subunit of voltage-gated calcium channels may carry a risk of abuse. To evaluate the abuse potential of crisugabalin, five well-recognized animal models were utilized in these preclinical studies. Firstly, an intravenous self-administration paradigm was implemented in rats that were self-administering propofol to assess the reinforcing effects of crisugabalin. Secondly, a rat drug discrimination study was employed to determine the pharmacological similarity between crisugabalin and the training drug midazolam. Then, a conditioned place preference (CPP) paradigm in rats was utilized to evaluate the rewarding properties of crisugabalin. After that, a spontaneous withdrawal study was conducted in rats chronically treated with crisugabalin to examine the liability of developing physical dependence. Finally, a mouse pentylenetetrazol-induced convulsion model was used following chronic exposure to crisugabalin to assess its potential for physical dependence. The results indicated that crisugabalin showed no positive reinforcing effects and did not display midazolam-like discriminative stimulus effects. Moreover, crisugabalin did not induce significant CPP in rats and there was no risk of physical dependence in the pentylenetetrazol-induced convulsion model. In the rat spontaneous withdrawal study, crisugabalin demonstrated a very low level of physical dependence. These findings suggest that crisugabalin has minimal to no potential for abuse, thereby establishing itself as a safer option relative to pregabalin and mirogabalin.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"252 ","pages":"Article 174015"},"PeriodicalIF":3.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Prenatal maternal stress induces increased avoidance behavior in adolescent mice offspring 产前母性压力诱导青春期小鼠后代的回避行为增加

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-04-30 DOI: 10.1016/j.pbb.2025.174029

Xueyong Yin , Rui Jiang , Xiaoyu Liu , Yiran Liu , Xiao Liu , Fei Zhou , Xi Yu , Shu Yan , Yunluo Li , Yuru Du , Youdong Li , Kaoqi Lian , Ye Zhao , Haishui Shi

Defensive behavior is an instinctive response to potential or actual threats, crucial for the survival and reproduction of species. It is influenced by both genetic and environmental factors and undergoes continuous changes throughout an individual's development. Stress, as a significant environmental factor, has a profound and enduring impact on reshaping an individual's behavior, particularly when experienced during early life. However, the effects of early life stress on defensive behavior remain unclear. In this study, defensive behaviors were evaluated in adolescent mice offspring exposed to prenatal stress. Serum corticosterone and neural dendritic spine density were measured. Behaviors results showed that prenatal stress significantly increased anxiety-like and avoidance behaviors in male offspring mice. Enzyme-linked immunosorbent assay (ELISA) results indicated that prenatal stress led to a significant increase in serum corticosterone levels in male offspring following predator odor exposure. Golgi staining analysis revealed a decrease in neural dendritic spine density in the medial prefrontal cortex (mPFC) of offspring. These findings suggest that behavioral changes in offspring mice caused by prenatal stress may be related to alterations in corticosterone levels and neuronal structure. However, the causation and specific mechanisms require further investigation.

防御行为是对潜在或实际威胁的本能反应，对物种的生存和繁殖至关重要。它受到遗传和环境因素的影响，并在个体的发展过程中不断变化。压力，作为一个重要的环境因素，对重塑一个人的行为有着深远而持久的影响，尤其是在生命早期经历的时候。然而，早期生活压力对防御行为的影响尚不清楚。本研究评估了暴露于产前压力下的青春期小鼠后代的防御行为。测定血清皮质酮和神经树突棘密度。行为学结果显示，产前应激显著增加雄性子代小鼠的焦虑样行为和回避行为。酶联免疫吸附试验（ELISA）结果表明，产前应激导致雄性后代在捕食者气味暴露后血清皮质酮水平显著升高。高尔基染色分析显示后代内侧前额叶皮层（mPFC）神经树突棘密度降低。这些发现表明，由产前压力引起的后代小鼠的行为改变可能与皮质酮水平和神经元结构的改变有关。然而，其原因和具体机制有待进一步研究。

{"title":"Prenatal maternal stress induces increased avoidance behavior in adolescent mice offspring","authors":"Xueyong Yin , Rui Jiang , Xiaoyu Liu , Yiran Liu , Xiao Liu , Fei Zhou , Xi Yu , Shu Yan , Yunluo Li , Yuru Du , Youdong Li , Kaoqi Lian , Ye Zhao , Haishui Shi","doi":"10.1016/j.pbb.2025.174029","DOIUrl":"10.1016/j.pbb.2025.174029","url":null,"abstract":"<div><div>Defensive behavior is an instinctive response to potential or actual threats, crucial for the survival and reproduction of species. It is influenced by both genetic and environmental factors and undergoes continuous changes throughout an individual's development. Stress, as a significant environmental factor, has a profound and enduring impact on reshaping an individual's behavior, particularly when experienced during early life. However, the effects of early life stress on defensive behavior remain unclear. In this study, defensive behaviors were evaluated in adolescent mice offspring exposed to prenatal stress. Serum corticosterone and neural dendritic spine density were measured. Behaviors results showed that prenatal stress significantly increased anxiety-like and avoidance behaviors in male offspring mice. Enzyme-linked immunosorbent assay (ELISA) results indicated that prenatal stress led to a significant increase in serum corticosterone levels in male offspring following predator odor exposure. Golgi staining analysis revealed a decrease in neural dendritic spine density in the medial prefrontal cortex (mPFC) of offspring. These findings suggest that behavioral changes in offspring mice caused by prenatal stress may be related to alterations in corticosterone levels and neuronal structure. However, the causation and specific mechanisms require further investigation.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"252 ","pages":"Article 174029"},"PeriodicalIF":3.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

N-acetylcysteine enhances the antipsychotic effect of aripiprazole in the neurodevelopmental rat model of schizophrenia n -乙酰半胱氨酸增强阿立哌唑对精神分裂症大鼠神经发育模型的抗精神病作用

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-04-30 DOI: 10.1016/j.pbb.2025.174028

Zofia Rogóż , Kinga Kamińska , Agnieszka Wąsik

Symptoms of schizophrenia are well characterized, but the mechanism underlying the pathogenesis of the disease still remains unknown. In addition, therapy of negative symptoms and cognitive deficits in schizophrenic patients is a serious clinical problem. Some clinical studies have shown that the atypical antipsychotic drug aripiprazole (ARI), and the antioxidant N-acetylcysteine (NAC) are effective in reducing positive and negative symptoms of schizophrenia in patients. The aim of the present study was to evaluate the influence of repeated co-treatment with low doses of ARI and NAC on the schizophrenia-like behavior in adult rats. The schizophrenia-like behavior was induced in Sprague-Dawley male pups in the neonatal days p5-p16 by repeated administration of the glutathione synthesis inhibitor L-butionine-(S,R)-sulfoximine (BSO) given together with the dopamine reuptake inhibitor 1-[2-[Bis-4(fluorophenyl)methoxy]ethyl]-4–3-(3-phenylpropyl) (GBR 12909). Adult rats received repeated co-treatment with ARI (0.1 mg/kg) and NAC (10 mg/kg) for 21 days, and their effects on schizophrenia-like behavior were assessed (on p90–91) using the social interaction test and novel object recognition test. The present data indicated that the studied drugs at higher doses: ARI (0.3 mg/kg but not 0.1 mg/kg) and NAC (30 mg/kg but not 10 mg/kg) reversed schizophrenia-like symptoms in the tested model. Moreover, repeated co-treatment with low doses of ARI with NAC also reversed schizophrenia-like behavior in the neurodevelopmental rat model of schizophrenia. The above results indicated that NAC enhanced the action of ARI in the used neurodevelopmental rat model of schizophrenia, and the mechanism of action of the used drugs in this model is discussed.

精神分裂症的症状有很好的特征，但其发病机制仍不清楚。此外，治疗精神分裂症患者的阴性症状和认知缺陷是一个严重的临床问题。一些临床研究表明，非典型抗精神病药物阿立哌唑（ARI）和抗氧化剂n -乙酰半胱氨酸（NAC）可有效减轻精神分裂症患者的阳性和阴性症状。本研究旨在评价低剂量ARI和NAC反复联合治疗对成年大鼠精神分裂症样行为的影响。用谷胱甘肽合成抑制剂L-butionine-(S，R)-亚砜亚胺（BSO）与多巴胺再摄取抑制剂1-[2-[Bis-4（氟苯基）甲氧基]乙基]-4 - 3-（3-苯基丙基）（GBR 12909）联合给药，可诱导Sprague-Dawley雄性幼崽在新生儿期（p5-p16）出现精神分裂症样行为。用ARI （0.1 mg/kg）和NAC （10 mg/kg）联合治疗成年大鼠21天，通过社会互动测试和新物体识别测试评估其对精神分裂症样行为的影响（p90-91）。目前的数据表明，较高剂量的研究药物：ARI （0.3 mg/kg，而不是0.1 mg/kg）和NAC （30 mg/kg，而不是10 mg/kg）在被试模型中逆转了精神分裂症样症状。此外，低剂量ARI与NAC反复联合治疗也逆转了精神分裂症神经发育大鼠模型中的精神分裂症样行为。上述结果表明，NAC可增强精神分裂症神经发育大鼠模型中ARI的作用，并对该模型中所用药物的作用机制进行探讨。

{"title":"N-acetylcysteine enhances the antipsychotic effect of aripiprazole in the neurodevelopmental rat model of schizophrenia","authors":"Zofia Rogóż , Kinga Kamińska , Agnieszka Wąsik","doi":"10.1016/j.pbb.2025.174028","DOIUrl":"10.1016/j.pbb.2025.174028","url":null,"abstract":"<div><div>Symptoms of schizophrenia are well characterized, but the mechanism underlying the pathogenesis of the disease still remains unknown. In addition, therapy of negative symptoms and cognitive deficits in schizophrenic patients is a serious clinical problem. Some clinical studies have shown that the atypical antipsychotic drug aripiprazole (ARI), and the antioxidant <em>N</em>-acetylcysteine (NAC) are effective in reducing positive and negative symptoms of schizophrenia in patients. The aim of the present study was to evaluate the influence of repeated co-treatment with low doses of ARI and NAC on the schizophrenia-like behavior in adult rats. The schizophrenia-like behavior was induced in Sprague-Dawley male pups in the neonatal days p5-p16 by repeated administration of the glutathione synthesis inhibitor L-butionine-(<em>S,R</em>)-sulfoximine (BSO) given together with the dopamine reuptake inhibitor 1-[2-[Bis-4(fluorophenyl)methoxy]ethyl]-4–3-(3-phenylpropyl) (GBR 12909). Adult rats received repeated co-treatment with ARI (0.1 mg/kg) and NAC (10 mg/kg) for 21 days, and their effects on schizophrenia-like behavior were assessed (on p90–91) using the social interaction test and novel object recognition test. The present data indicated that the studied drugs at higher doses: ARI (0.3 mg/kg but not 0.1 mg/kg) and NAC (30 mg/kg but not 10 mg/kg) reversed schizophrenia-like symptoms in the tested model. Moreover, repeated co-treatment with low doses of ARI with NAC also reversed schizophrenia-like behavior in the neurodevelopmental rat model of schizophrenia. The above results indicated that NAC enhanced the action of ARI in the used neurodevelopmental rat model of schizophrenia, and the mechanism of action of the used drugs in this model is discussed.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"252 ","pages":"Article 174028"},"PeriodicalIF":3.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Different protocols of REM sleep deprivation led to controversial effects on OCD- and anxiety-like behaviors and locomotor activity in fear conditioning male and female rats with respect to BDNF expression level 不同的快速眼动睡眠剥夺方案导致恐惧条件下的雄性和雌性大鼠在BDNF表达水平方面对强迫症和焦虑样行为和运动活动的影响存在争议

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-04-30 DOI: 10.1016/j.pbb.2025.174027

Masoumeh Payamani , Seyedeh-Tabassom Abdollahi-Keyvani , Mandana Sajjadi , Shahin Akhondzadeh , Reihane Javid , Reihaneh Nakhaei-Zadeh , Marzieh Jalalian-Javadpour , Salar Vaseghi

Specific protocols of rapid-eye movement (REM) sleep deprivation (SD) may lead to behavioral phenotypes considered as obsessive-compulsive disorder (OCD)-like behavior and hyperactivity (mania-like behavior). The present study aimed to assess the effects of REM SD on both sexes of control and fear conditioning (FC) rats. REM SD was induced for 1 or 2 or 3 weeks (6 h/d). Freezing, locomotor activity, anxiety-like behavior, grooming and burying marbles (OCD-like behaviors), and brain-derived neurotrophic factor (BDNF) in the hippocampus were evaluated. The results showed 1w REM SD decreased freezing in females, while 2w and 3w REM SD decreased freezing in both sexes. Locomotor activity in 2w REM SD males was increased, while was decreased in 3w group. In females, both 2w and 3w REM SD increased locomotion. REM SD in both sexes increased locomotion in FC rats. All REM SD protocols decreased anxiety in both sexes of FC rats. REM SD in control and FC rats led to OCD-like behaviors. All REM SD protocols decreased BDNF in both sexes, while 3w slightly increased it, suggesting a compensatory mechanism over time. 2w and 3w REM SD increased BDNF in FC rats in both sexes. Pearson correlation test also showed that changes in BDNF levels may be related to some behavioral changes only in females. In conclusion, for the first time, the present study showed sex differences in the effects of REM SD on behavioral functions in control and FC rats, and in the relationship between BDNF levels and behavioral changes.

快速眼动（REM）睡眠剥夺（SD）的特定协议可能导致被认为是强迫症（OCD）样行为和多动（躁狂样行为）的行为表型。本研究旨在评估快速眼动SD对两性控制和恐惧条件反射（FC）大鼠的影响。快速眼动SD诱导1、2、3周（6 h/d）。评估冻结、运动活动、焦虑样行为、梳理和掩埋弹珠（强迫症样行为）以及海马脑源性神经营养因子（BDNF）。结果显示，1w快速眼动SD降低了女性的冻结，而2w和3w快速眼动SD降低了两性的冻结。2w组运动活动增加，3w组运动活动减少。在女性中，2w和3w的REM SD都增加了运动。两性的快速眼动SD均增加了FC大鼠的运动。所有快速眼动SD方案均能降低FC大鼠的焦虑。对照大鼠和FC大鼠的REM SD导致了类似强迫症的行为。所有快速眼动SD方案都降低了两性的BDNF，而3w略有增加，这表明随着时间的推移存在一种补偿机制。2w和3w REM SD均使FC大鼠BDNF增加。Pearson相关检验还表明，BDNF水平的变化可能只与女性的某些行为变化有关。综上所述，本研究首次揭示了REM SD对对照大鼠和FC大鼠行为功能影响的性别差异，以及BDNF水平与行为改变的关系。

{"title":"Different protocols of REM sleep deprivation led to controversial effects on OCD- and anxiety-like behaviors and locomotor activity in fear conditioning male and female rats with respect to BDNF expression level","authors":"Masoumeh Payamani , Seyedeh-Tabassom Abdollahi-Keyvani , Mandana Sajjadi , Shahin Akhondzadeh , Reihane Javid , Reihaneh Nakhaei-Zadeh , Marzieh Jalalian-Javadpour , Salar Vaseghi","doi":"10.1016/j.pbb.2025.174027","DOIUrl":"10.1016/j.pbb.2025.174027","url":null,"abstract":"<div><div>Specific protocols of rapid-eye movement (REM) sleep deprivation (SD) may lead to behavioral phenotypes considered as obsessive-compulsive disorder (OCD)-like behavior and hyperactivity (mania-like behavior). The present study aimed to assess the effects of REM SD on both sexes of control and fear conditioning (FC) rats. REM SD was induced for 1 or 2 or 3 weeks (6 h/d). Freezing, locomotor activity, anxiety-like behavior, grooming and burying marbles (OCD-like behaviors), and brain-derived neurotrophic factor (BDNF) in the hippocampus were evaluated. The results showed 1w REM SD decreased freezing in females, while 2w and 3w REM SD decreased freezing in both sexes. Locomotor activity in 2w REM SD males was increased, while was decreased in 3w group. In females, both 2w and 3w REM SD increased locomotion. REM SD in both sexes increased locomotion in FC rats. All REM SD protocols decreased anxiety in both sexes of FC rats. REM SD in control and FC rats led to OCD-like behaviors. All REM SD protocols decreased BDNF in both sexes, while 3w slightly increased it, suggesting a compensatory mechanism over time. 2w and 3w REM SD increased BDNF in FC rats in both sexes. Pearson correlation test also showed that changes in BDNF levels may be related to some behavioral changes only in females. In conclusion, for the first time, the present study showed sex differences in the effects of REM SD on behavioral functions in control and FC rats, and in the relationship between BDNF levels and behavioral changes.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"252 ","pages":"Article 174027"},"PeriodicalIF":3.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143898716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0