Pharmacology Biochemistry and Behavior最新文献_第7页

Dissociating the incubation of appetitive and consummatory behavior in a model of oral cocaine self-administration 在口服可卡因自我给药模型中分离食欲和圆满行为的潜伏期

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-06-27 DOI: 10.1016/j.pbb.2025.174055

Mark D. Namba , Samuel L. Goldberg , Christine M. Side , Abhiram Yadlapalli , Christina M. Curran-Alfaro , Devin Kress , Melissa F. Fogarty , Amanda L.A. Mohr , Jacqueline M. Barker

Cocaine use disorder remains a persistent public health dilemma that currently lacks effective treatment strategies. One key impediment to successful treatment outcomes is increased drug craving that occurs over the course of abstinence and subsequent relapse to drug use. This phenomenon, known as the incubation of drug craving, has been modeled extensively in rodent models of intravenous drug self-administration. The design of most intravenous self-administration studies examining the incubation effect precludes disentangling appetitive and consummatory behaviors as drug seeking (appetitive) and taking (consummatory) is simultaneous. Here, we employed a model of oral cocaine self-administration to interrogate the incubation of drug vs nondrug craving, where the route of administration is identical between reinforcers and appetitive and consummatory behaviors are dissociable. Oral self-administration of cocaine produced detectable levels of cocaine and its metabolite, benzoylecgonine, within the blood and brain, and tissue levels of both substrates correlated with cocaine consumption. When tested for seeking- (lever pressing) and taking-related (magazine head entries) behavior after 1 or 21 days of forced abstinence, we observed incubation of lever pressing among cocaine-administering mice and incubation of magazine entries among saccharin-administering mice. These behavioral changes were accompanied by reduced expression of the glial glutamate transporter GLT-1 within the nucleus accumbens (NAc) of cocaine self-administering mice, regardless of abstinence. Altogether, these results underscore the utility of this model of cocaine self-administration, highlight the conserved nature of incubated cocaine seeking across routes of administration, and demonstrate the dissociable neurobehavioral sequelae of the incubation of reward seeking across reinforcer types.

可卡因使用障碍仍然是一个长期存在的公共卫生难题，目前缺乏有效的治疗策略。成功治疗结果的一个关键障碍是在戒断过程中出现的药物渴望增加以及随后的药物使用复发。这种现象被称为药物渴望的潜伏期，在啮齿类动物的静脉注射药物自我给药模型中得到了广泛的模拟。大多数静脉内自我给药研究的设计，检验了潜伏效应，排除了食欲和满足行为的分离，因为药物寻找（食欲）和服用（满足）是同时发生的。在本研究中，我们采用了一个口服可卡因自我给药模型来研究药物和非药物渴望的潜伏期，其中强化物的给药途径是相同的，而食欲和圆满行为是可分离的。口服自用可卡因可在血液和大脑中产生可检测水平的可卡因及其代谢物苯甲酰冈碱，这两种底物的组织水平与可卡因的消耗相关。在强迫戒断1天或21天后，我们对寻找（按杠杆）和拿取相关（杂志头条目）行为进行了测试，我们观察到可卡因小鼠按杠杆的潜伏期和糖精小鼠按杂志头条目的潜伏期。这些行为变化伴随着可卡因自我给药小鼠伏隔核（NAc）内神经胶质谷氨酸转运体GLT-1的表达减少，与戒断无关。总之，这些结果强调了这种可卡因自我给药模式的实用性，强调了可卡因寻求在不同给药途径中孵育的保守性，并证明了奖励寻求在不同强化物类型中孵育的可分离的神经行为后遗症。

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引用次数: 0

TRPV1 deletion enhances consumption but not seeking behavior for sweetened nicotine solution in male mice TRPV1缺失增加了雄性小鼠对甜味尼古丁溶液的消费，但不寻求行为。

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-06-26 DOI: 10.1016/j.pbb.2025.174054

Salma Tannous, Florence Darlot, Yoan Salafranque, Martine Cador, Stephanie Caille

Nicotine is not only the primary addictive component of smoking but it also greatly contributes to the sensory properties of tobacco. Consequently, investigating the orosensory effects of nicotine is essential to understand the vulnerability to initial stages of cigarette smoking. Within the oral cavity, transient receptor potential vanilloid 1 receptors (TRPV1Rs) are responsible for sensations such as chili peppers-induced pungency and oral burning, and these receptors are activated by nicotine. Here, we hypothesized that TRPV1Rs contribute to the irritant and burning sensations induced by nicotine, and that its dysfunction may promote vulnerability to nicotine addiction. To test this, adult male mice with invalidation of the TRPV1R gene were exposed to oral self-administration of nicotine solution allowing us to examine the key steps of the addictive process, namely acquisition and maintenance of taking behavior, motivation to obtain the drug and nicotine seeking behavior. We found that in comparison to wild-type mice, knockout (KO) mice consumed significantly higher amounts of nicotine both at the training dose and across the dose-response curve. Despite the increased consumption of nicotine by KO mice, this did not promote greater motivational properties of nicotine or cue-induced reinstatement of drug-seeking behavior in the absence of reinforcer. Altogether, these results suggest that decreased function of the TRPV1Rs prevents the development of aversion to nicotine solution, which may contribute to a heightened vulnerability to nicotine initiation.

尼古丁不仅是吸烟的主要成瘾性成分，而且对烟草的感官特性也有很大影响。因此，研究尼古丁对口腔感官的影响对于了解吸烟初期的脆弱性至关重要。在口腔内，瞬时受体电位香草样蛋白1受体（TRPV1Rs）负责辣椒引起的辛辣和口腔灼烧等感觉，这些受体被尼古丁激活。在这里，我们假设TRPV1Rs参与尼古丁引起的刺激和灼烧感觉，其功能障碍可能促进尼古丁成瘾的易感性。为了验证这一点，我们将TRPV1R基因失效的成年雄性小鼠暴露于口服尼古丁溶液中，让我们检查成瘾过程的关键步骤，即获取和维持服用行为、获得药物的动机和尼古丁寻求行为。我们发现，与野生型小鼠相比，敲除小鼠在训练剂量和剂量-反应曲线上消耗的尼古丁量都要高得多。尽管KO小鼠的尼古丁摄入量增加，但在缺乏强化物的情况下，这并没有促进尼古丁的更大动机特性或线索诱导的药物寻求行为的恢复。综上所述，这些结果表明，TRPV1Rs功能的下降阻止了尼古丁溶液厌恶的发展，这可能有助于提高尼古丁引发的易感性。

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引用次数: 0

Cannabigerol does not affect contextual fear memory in mice but modulates nociception in a sex-dependent manner 大麻酚不影响小鼠的情境恐惧记忆，但以性别依赖的方式调节伤害感受。

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-06-14 DOI: 10.1016/j.pbb.2025.174053

Julia P. Andreotti , Lia P. Iglesias , Rayssa C. Briânis , Walace C.P. Barra , Igor D.G. Duarte , Cristina A.J. Stern , Leandro J. Bertoglio , José A. Crippa , Daniele C. Aguiar , Fabrício A. Moreira

Conditioned fear is a response to contexts or cues previously paired with aversive stimuli. Substances from the herb Cannabis sativa (phytocannabinoids), such as cannabidiol (CBD), prevent fear responses and hold potential as new treatments for certain psychiatric disorders, such as post-traumatic stress disorder. The phytocannabinoid cannabigerol (CBG), similarly to CBD, lacks psychotomimetic effects and targets multiple receptors involved in fear-related pathways. This study tested the hypothesis that CBG inhibits memory acquisition, consolidation, and retrieval/expression in contextual fear conditioning (CFC) in both male and female C57BL/6 J mice. We also characterized CBG for its activity upon nociceptive and motor responses. Animals were submitted to CFC protocols and CBG (3, 10, or 30 mg/kg) was administered at different timepoints to assess its effect in each memory phase. CBG failed to significantly change the acquisition, consolidation or retrieval/expression of contextual fear memories. Because CFC relies on nociceptive stimuli (shocks), we also evaluated the effects of CBG on the tail-flick test. A biphasic antinociceptive effect occurred 30 min after drug administration in female animals, in which the doses of 3 mg/kg and 30 mg/kg, respectively, increased and reduced the latency for withdrawal response. Finally, no motor impairment was observed in the rotarod test either 30 or 120 min after CBG administration. In summary, CBG (3–30 mg/kg) failed to interfere with CFC in male and female mice, although it induced a biphasic effect on nociceptive response. Future experiments should investigate the role of this substance in different protocols, memory phases, and aversive memory models.

条件性恐惧是对先前与厌恶刺激配对的环境或线索的反应。大麻二酚（CBD）等草本植物大麻素中的物质可以预防恐惧反应，并有可能成为某些精神疾病（如创伤后应激障碍）的新疗法。与CBD类似，植物大麻素大麻igerol （CBG）缺乏拟精神作用，并针对涉及恐惧相关途径的多个受体。本研究在雄性和雌性C57BL/6 J小鼠中验证了CBG抑制情境恐惧条件反射（CFC）记忆获取、巩固和检索/表达的假设。我们还描述了CBG对伤害和运动反应的活性。将动物提交到CFC方案中，并在不同时间点给予CBG(3,10或30 mg/kg)，以评估其在每个记忆阶段的效果。CBG不能显著改变情境恐惧记忆的获取、巩固或提取/表达。由于CFC依赖于伤害性刺激（冲击），我们也评估了CBG在甩尾测试中的作用。雌性动物在给药30 min后出现双相抗伤害感受效应，分别给药3 mg/kg和30 mg/kg可增加和减少戒断反应潜伏期。最后，在CBG给药后30或120 min的旋转杆试验中未观察到运动障碍。综上所述，CBG（3-30 mg/kg）对雄性和雌性小鼠的CFC没有干扰作用，尽管它对伤害性反应有双相影响。未来的实验应该研究这种物质在不同协议、记忆阶段和厌恶记忆模型中的作用。

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引用次数: 0

Xylazine co-administration influences the rewarding properties of heroin and withdrawal in male rats 二甲肼对雄性大鼠海洛因奖赏性和戒断行为的影响。

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-06-10 DOI: 10.1016/j.pbb.2025.174052

Mason Hochstetler , Anastasia Dodge , Songjukta Chakraborty , Ann Jeffers , Swarup Mitra

The current opioid use disorder crisis has been further complicated by the adulteration of the drug supply with the veterinary sedative xylazine. Xylazine is not approved for human use and is associated with numerous adverse effects when consumed. While most existing research has examined the consequences of fentanyl-xylazine co-administration, to date, no studies have explored the behavioral and withdrawal effects of heroin-xylazine co-administration. In the current study, we used a contingent model of heroin-xylazine (0.02 and 0.15 mg/kg/infusion) co-administration to demonstrate that in male rats, heroin consumption and motivation are attenuated when xylazine is co-administered with heroin. However, co-administration with xylazine potentiated cue-induced drug-seeking behavior following 10 days of extinction. In a separate cohort, we evaluated the impact of our selected xylazine dose on locomotion and found that it did not induce sedation, implicating that the behavioral effects produced were not confounded by locomotor suppression. We also assessed naloxone-precipitated withdrawal (1 mg/kg, s.c) and observed a reduction in total somatic withdrawal signs in the heroin-xylazine group, an effect not seen in the heroin-only group. Surprisingly, these reduced somatic signs did not extend to all behavioral modalities and diverged based on the type of somatic signs. These findings suggest that xylazine may function as a satiety-enhancing agent when co-administered with heroin, as evidenced by the suppression of self-administration. However, xylazine's effect on precipitating cue-induced reinstatement reveals the synergistic potential of its adulteration during relapse.

目前的阿片类药物使用障碍危机已进一步复杂化与兽药镇静剂二甲肼掺假的药物供应。噻嗪未被批准用于人类使用，并且在食用时会产生许多不良反应。虽然大多数现有的研究已经检查了芬太尼-羟嗪共给药的后果，但迄今为止，还没有研究探索了海洛因-羟嗪共给药的行为和戒断效应。在目前的研究中，我们使用了一个海洛因-羟嗪（0.02和0.15 mg/kg/输注）联合给药的偶然模型来证明，在雄性大鼠中，羟嗪和海洛因联合给药时，海洛因的消耗和动机都减弱了。然而，在10 天的消失后，与xylazine共同给药增强了线索诱导的药物寻求行为。在一个单独的队列中，我们评估了我们选择的噻嗪剂量对运动的影响，发现它不会诱导镇静，这意味着所产生的行为效应不会与运动抑制相混淆。我们还评估了纳洛酮沉淀戒断（1 mg/kg, s.c），并观察到海洛因-羟嗪组总体戒断症状的减少，这在海洛因组中没有出现。令人惊讶的是，这些减少的躯体体征并没有扩展到所有的行为模式，而是根据躯体体征的类型而分化。这些发现表明，当与海洛因共同给药时，噻嗪可能具有增强饱腹感的作用，这一点可以通过抑制自我给药得到证明。然而，二甲肼对诱发的诱发性恢复的作用揭示了其在复发期间掺假的协同作用。

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引用次数: 0

Prenatal serotonin depletion persistently disrupts social behavior and modulates ΔFosB and SERT expression in mice 产前血清素耗竭持续破坏小鼠的社会行为并调节ΔFosB和SERT表达。

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-05-30 DOI: 10.1016/j.pbb.2025.174043

María Carolina Fabio , María Victoria Mujica , Elisa Fogliatti , María Victoria Aguilar , Alicia Laura Degano , Ricardo Marcos Pautassi

Embryonic fluctuations in serotonin (5-HT) levels during pregnancy have been associated with maternal depression and linked to social deficits and neuropsychiatric disorders in offspring. This preclinical study examined the long-term effects of transient prenatal 5-HT depletion on social, anxiety-like, and depressive-like behaviors across development, and evaluated associated changes in serotonergic markers and neuronal activity in key brain regions.

Pregnant C57BL/6 mice were administered the 5-HT synthesis inhibitor para-chlorophenylalanine (PCPA), or its vehicle, from gestational day 12.5 to 14.5. Maternal affect and caregiving behavior were assessed postnatally, and offspring of both sexes were evaluated for social interaction, compulsive behavior, locomotion, ultrasonic vocalizations, and helplessness during infancy, adolescence, and adulthood. Immunohistochemistry was performed in the offspring to assess serotonin transporter (SERT) and ΔFosB expression in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc).

PCPA administration did not significantly alter depressive- or anxiety-like behavior in the dams, nor did it significantly affect maternal caregiving. The offspring prenatally exposed to PCPA exhibited reduced social interaction and increased non-social behaviors compared to controls during adolescence and adulthood. Prenatal serotonin depletion also led to decreased SERT and ΔFosB expression in the mPFC and NAc, indicating disrupted serotonergic signaling and altered neuronal activity in mood- and reward-related brain regions.

The findings suggest that even brief disruptions of serotonergic signaling during gestation can induce lasting social deficits and neurobiological alterations relevant to the pathophysiology of neurodevelopmental disorders.

怀孕期间胚胎血清素（5-HT）水平的波动与母亲抑郁有关，并与后代的社交缺陷和神经精神障碍有关。这项临床前研究检查了短暂的产前5-羟色胺缺失对发育过程中社交、焦虑样和抑郁样行为的长期影响，并评估了大脑关键区域5-羟色胺能标记物和神经元活动的相关变化。妊娠C57BL/6小鼠在妊娠12.5 ~ 14.5天给予5-羟色胺合成抑制剂对氯苯丙氨酸（PCPA）或其载体。在出生后评估母亲的情感和照顾行为，并评估两性后代在婴儿期、青春期和成年期的社会互动、强迫行为、运动、超声波发声和无助感。对后代进行免疫组化，以评估血清素转运体（SERT）和ΔFosB在内侧前额叶皮层（mPFC）和伏隔核（NAc）中的表达。PCPA给药并没有显著改变母鼠的抑郁或焦虑样行为，也没有显著影响母鼠的照料。与对照组相比，产前暴露于PCPA的后代在青春期和成年期表现出较少的社会互动和增加的非社会行为。产前血清素缺失也导致mPFC和NAc中SERT和ΔFosB表达降低，表明血清素能信号被破坏，情绪和奖励相关脑区神经元活动改变。研究结果表明，即使是妊娠期血清素信号的短暂中断也会导致持久的社会缺陷和与神经发育障碍病理生理学相关的神经生物学改变。

{"title":"Prenatal serotonin depletion persistently disrupts social behavior and modulates ΔFosB and SERT expression in mice","authors":"María Carolina Fabio , María Victoria Mujica , Elisa Fogliatti , María Victoria Aguilar , Alicia Laura Degano , Ricardo Marcos Pautassi","doi":"10.1016/j.pbb.2025.174043","DOIUrl":"10.1016/j.pbb.2025.174043","url":null,"abstract":"<div><div>Embryonic fluctuations in serotonin (5-HT) levels during pregnancy have been associated with maternal depression and linked to social deficits and neuropsychiatric disorders in offspring. This preclinical study examined the long-term effects of transient prenatal 5-HT depletion on social, anxiety-like, and depressive-like behaviors across development, and evaluated associated changes in serotonergic markers and neuronal activity in key brain regions.</div><div>Pregnant C57BL/6 mice were administered the 5-HT synthesis inhibitor para-chlorophenylalanine (PCPA), or its vehicle, from gestational day 12.5 to 14.5. Maternal affect and caregiving behavior were assessed postnatally, and offspring of both sexes were evaluated for social interaction, compulsive behavior, locomotion, ultrasonic vocalizations, and helplessness during infancy, adolescence, and adulthood. Immunohistochemistry was performed in the offspring to assess serotonin transporter (SERT) and ΔFosB expression in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc).</div><div>PCPA administration did not significantly alter depressive- or anxiety-like behavior in the dams, nor did it significantly affect maternal caregiving. The offspring prenatally exposed to PCPA exhibited reduced social interaction and increased non-social behaviors compared to controls during adolescence and adulthood. Prenatal serotonin depletion also led to decreased SERT and ΔFosB expression in the mPFC and NAc, indicating disrupted serotonergic signaling and altered neuronal activity in mood- and reward-related brain regions.</div><div>The findings suggest that even brief disruptions of serotonergic signaling during gestation can induce lasting social deficits and neurobiological alterations relevant to the pathophysiology of neurodevelopmental disorders.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"253 ","pages":"Article 174043"},"PeriodicalIF":3.3,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199842","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

Population-dependent impacts of para-chlorophenylalanine, a tryptophan hydroxylase inhibitor, on homebase formation and thigmotaxis in adult zebrafish 对氯苯丙氨酸（一种色氨酸羟化酶抑制剂）对成年斑马鱼母碱形成和吸氧性的种群依赖性影响

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.2025.174042

Cássio M. Resmim , João V. Borba , Rossano M. Silva , Hevelyn S. Moraes , Camilla W. Pretzel , Julia Canzian , Barbara D. Fontana , Maribel A. Rubin , Eduardo P. Rico , Matthew O. Parker , Denis B. Rosemberg

Alterations in monoamine levels, such as serotonin, play a role in the pathophysiology of affective disorders. Para-chlorophenylalanine (pCPA), a tryptophan hydroxylase inhibitor, impairs serotonin synthesis and increases anxiety-like behaviors in various species. Outbred zebrafish population, such as short fin (SF) and leopard (LEO), differ in serotonin expression, habituation patterns, and responses to novel environments. Locomotor and exploratory profiles are strongly influenced by homebase behavior, which can be assessed in the open field test (OFT). To further investigate a putative role of the serotoninergic system in homebase formation and exploratory behavior dynamics, we administered pCPA to two zebrafish populations (SF and LEO) with distinct anxiety profiles and homebase occupancy. Fish received intraperitoneal injections of pCPA (300 mg/kg) or vehicle for two consecutive days, followed by a 30-min OFT 24 h later. Both pCPA-treated populations showed increased locomotion and periphery occupancy was elevated during the habituation period (first 15 min of testing). Although pCPA did not alter homebase-related behaviors in LEO, the SF population exhibited a delayed homebase formation, likely due to disrupted exploratory-related mechanisms. Furthermore, Principal Component Analysis (PCA) and K-means clustering revealed that behaviors related to periphery occupancy and distance traveled accounted for approximately 80 % of the observed data variability. Collectively, our data show that pCPA impairs homebase formation, with stronger effects in SF fish and increases thigmotaxis. Overall, these results suggest that pCPA disrupts the organization of exploratory behavior, particularly the habituation processes, probably associated with anxiety-like phenotypes.

单胺水平的改变，如血清素，在情感性障碍的病理生理中起作用。对氯苯丙氨酸（pCPA）是一种色氨酸羟化酶抑制剂，在各种物种中损害血清素合成并增加焦虑样行为。近亲繁殖的斑马鱼种群，如短鳍（SF）和豹纹（LEO），在血清素表达、适应模式和对新环境的反应方面存在差异。本垒行为对运动和探索剖面有很大影响，这可以在野外测试（OFT）中进行评估。为了进一步研究血清素能系统在本垒形成和探索性行为动力学中的作用，我们对两个具有不同焦虑特征和本垒占用的斑马鱼种群（SF和LEO）进行了pCPA治疗。鱼连续两天腹腔注射pCPA （300 mg/kg）或载体，24小时后进行30分钟的OFT。在习惯化期间（测试的前15分钟），两个pppa处理的种群都表现出运动增加和外围占用率升高。尽管pCPA没有改变LEO中与本垒相关的行为，但SF群体表现出本垒形成的延迟，可能是由于探索相关机制的破坏。此外，主成分分析（PCA）和K-means聚类表明，与周边占用和行驶距离相关的行为约占观察到的数据变异性的80%。总的来说，我们的数据表明，pCPA损害了本垒的形成，对SF鱼的影响更大，并增加了移植物性。总的来说，这些结果表明，pCPA破坏了探索行为的组织，特别是习惯化过程，可能与焦虑样表型有关。

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引用次数: 0

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。

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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。

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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。

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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。

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引用次数: 0