Pharmacology Biochemistry and Behavior最新文献_第9页

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 : 2025-07-01 Epub 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。

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引用次数: 0

The ventral hippocampus mediates experience-dependent social modulation of fear in rats 腹侧海马体介导大鼠恐惧的经验依赖性社会调节

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-07-01 Epub Date: 2025-04-23 DOI: 10.1016/j.pbb.2025.174016

Dan Tao , Cuijie Shi , Zhihao Song , Jing Wen , Yujun Gao , Yixiao Luo , Haishui Shi , Shihao Huang

Fear Conditioning by Proxy (FCbP) is a form of socially mediated fear learning, in which no-conditioned rodents acquire fear memories through social interactions with fear-conditioned rodents. This study investigates the impact of prior similar experiences on the transmission of contextual fear memories in FCbP and explores the role of the ventral hippocampus (vHPC) in the social transmission of fear. Observers were divided into two groups: those with contextual experience (D/O) and those without contextual experience- naïve (O). These rats were exposed to fear-conditioned demonstrators (D) through social interaction, and their responses to fear contexts were observed. Additionally, the effect of vHPC inactivation on fear memory transmission was examined by injecting lidocaine into the vHPC. Fear was transmitted through social interaction among experienced rats but not among naive rats. Furthermore, lidocaine injection into the vHPC inhibited the social transmission of fear memories among experienced rats. This study demonstrates that contextual fear memories can be transmitted through social interaction among experience-dependent rats but not among naive rats. That inactivation in the vHPC blocks the social transmission of contextual fear memories.

代理恐惧条件反射（FCbP）是一种社会中介的恐惧学习形式，无条件啮齿动物通过与恐惧条件啮齿动物的社会互动获得恐惧记忆。本研究探讨了前相似经历对情境恐惧记忆在FCbP中传递的影响，并探讨了腹侧海马体（vHPC）在恐惧社会传递中的作用。将观察者分为有情境经验（D/O）和无情境经验（naïve）两组，通过社会互动将大鼠暴露于恐惧条件示威者(D)中，观察其对恐惧情境的反应。此外，通过在vHPC内注射利多卡因，观察vHPC失活对恐惧记忆传递的影响。恐惧在经验丰富的大鼠中通过社会互动传播，而在幼稚的大鼠中则没有。此外，利多卡因注射到vHPC抑制恐惧记忆在经验大鼠之间的社会传递。本研究表明，情境恐惧记忆在经验依赖大鼠中可以通过社会互动进行传递，而在幼稚大鼠中则不能。vHPC的失活阻断了情境恐惧记忆的社会传播。

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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 : 2025-07-01 Epub 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。

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引用次数: 0

The dosage-dependent effects of cevimeline in preventing clozapine-induced dyslipidaemia in female rats 西维美林预防氯氮平诱导的雌性大鼠血脂异常的剂量依赖性作用

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-07-01 Epub Date: 2025-04-18 DOI: 10.1016/j.pbb.2025.174017

Jiamei Lian , Bo Pan , Chao Deng

Clozapine is the most effective second-generation antipsychotic drug, especially for the therapy of treatment-resistant schizophrenia. However, it is associated with metabolic side-effects. Clozapine has a high antagonistic affinity to muscarinic M3 receptors, which has been reported to play a significant role in these side-effects. This study aimed to investigate whether co-administration of cevimeline (an M3 receptor agonist) could prevent the metabolic disorders induced by clozapine. Female Sprague Dawley rats were treated orally with clozapine (20 mg/kg, 3 times daily) and/or cevimeline at three dosages (3, 6, 9 mg/kg, 3 times daily), or a vehicle for two weeks. Body weight gain, food/water intake, and temperature were recorded. Open field tests were performed to assess motor activity. Clozapine only treatment significantly decreased body weight gain, feeding efficiency, perirenal, periovary, inguinal, total white fat mass, and NEFA levels. The reduction in body weight gain and feeding efficiency caused by clozapine was partially reversed by co-treatment with 3 or 6 mg/kg cevimeline. Clozapine also significantly increased the liver mass, LDL, and HDL level, which were reversed by the co-treatment with cevimeline at all tested dosages. These results support further clinical trials to evaluate cevimeline's potential in controlling clozapine-induced dyslipidemia.

氯氮平是最有效的第二代抗精神病药物，尤其适用于治疗难治性精神分裂症。然而，它与代谢副作用有关。氯氮平对毒蕈碱M3受体具有高度的拮抗亲和力，据报道，这在这些副作用中起重要作用。本研究旨在探讨西维美林（一种M3受体激动剂）是否可以预防氯氮平引起的代谢紊乱。雌性Sprague Dawley大鼠口服氯氮平（20 mg/kg，每日3次）和/或西维美林（3、6、9 mg/kg，每日3次），或给药2周。记录体重增加、食物/水摄入量和体温。进行开阔场试验以评估运动活动。仅氯氮平治疗可显著降低体重增加、喂养效率、肾周、骨膜、腹股沟、总白色脂肪量和NEFA水平。氯氮平引起的体重增加和摄食效率的降低可通过与3或6 mg/kg西维美林共同治疗部分逆转。氯氮平还显著增加了肝脏质量、LDL和HDL水平，而在所有测试剂量下，与西维美林共同治疗可以逆转这种情况。这些结果支持进一步的临床试验来评估西维美林在控制氯氮平诱导的血脂异常方面的潜力。

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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 : 2025-07-01 Epub 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。

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引用次数: 0

Simultaneous cocaine and ethanol self-administration promotes a sex-dimorphic pattern in drug-seeking behaviour and alters plasma amino acid profile related to glutamate homeostasis in young adult rats 同时服用可卡因和乙醇促进了年轻成年大鼠的觅药行为的性别二态模式，并改变了与谷氨酸稳态相关的血浆氨基酸谱。

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-06-01 Epub Date: 2025-03-08 DOI: 10.1016/j.pbb.2025.173988

Lucía Garrido-Matilla, Alberto Marcos, Natalia Puig-Martínez, Emilio Ambrosio

The concurrent use of cocaine and alcohol is highly prevalent in Western countries and carries a substantial risk of relapse in recovering process. Craving, characterized as a strong desire for consuming drugs, is a core feature of cocaine and ethanol use disorders and presents a significant challenge to maintaining abstinence and preventing relapse. The primary objective of this study was to explore the behavioural patterns associated with the incubation of drug-seeking for a cocaine-ethanol combination and, secondarily, to examine the plasma amino acid profile that might be associated with this combination. To achieve this, we employed an extended-access intravenous self-administration model over 10 sessions with both substances, followed by withdrawal periods of 2 and 30 days in young adult rats in both sexes. After the subsequent drug-seeking test, changes in plasma amino acid concentrations were examined. Cocaine and ethanol co-administration resulted in a lower consumption rate among rats compared to those consuming cocaine alone. However, both groups exhibited incubation of drug-seeking behaviour. Sex differences were observed in self-administration patterns and in the incubation of drug-seeking behaviour. Notably, after 30 days of withdrawal, alterations were detected in plasma levels of several amino acids, including glutamine, glycine, serine, threonine, and glutamate, which are associated with glutamate homeostasis. This study aims to contribute to our understanding of potential changes in the plasma amino acid profile in cocaine users who also consume ethanol, particularly during abstinence and craving incubation.

同时使用可卡因和酒精在西方国家非常普遍，在恢复过程中有很大的复发风险。渴望是吸食毒品的强烈欲望，是可卡因和乙醇使用障碍的核心特征，对保持戒断和防止复发提出了重大挑战。本研究的主要目的是探索与可卡因-乙醇组合药物寻找潜伏期相关的行为模式，其次是检查可能与这种组合相关的血浆氨基酸谱。为了实现这一目标，我们采用了一种延长静脉内自我给药的模型，在10个疗程中使用这两种物质，然后在年轻成年大鼠中分别有2天和30 天的停药期。在随后的药物寻找试验后，检测血浆氨基酸浓度的变化。与单独服用可卡因的大鼠相比，可卡因和乙醇共同服用导致大鼠的消费率较低。然而，两组都表现出寻求药物行为的潜伏期。在自我给药模式和寻求药物行为的潜伏期中观察到性别差异。值得注意的是，停药30 天后，血浆中几种氨基酸的水平发生了变化，包括谷氨酰胺、甘氨酸、丝氨酸、苏氨酸和谷氨酸，它们与谷氨酸稳态有关。本研究旨在帮助我们了解同时摄入乙醇的可卡因使用者血浆氨基酸谱的潜在变化，特别是在戒断和渴望潜伏期。

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引用次数: 0

Agomelatine with cognitive behavioral therapy reduces insomnia severity index and subjective units of distress scores than initial-dose clonazepam in moderate to severe insomnia patients: A quasi-experimental study 阿戈美拉汀联合认知行为疗法对中重度失眠症患者的失眠严重指数和主观痛苦评分比初始剂量氯硝西泮降低：一项准实验研究。

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-06-01 Epub Date: 2025-03-27 DOI: 10.1016/j.pbb.2025.174003

Kousalya Prabahar , Abinaya Ravikumar , Anu Priya Jeyabalan , Bharath Ravi , Chandini Ravikumar , Nithishadevi PannirukaiSelvan , Saleh F. Alqifari , Varadharajan Sivaraman , Natarajan Shanmugasundaram , Karthik Sankar

Background

Insomnia can be caused by various factors including lack of sleep, stress, sadness, hormonal changes, excessive caffeine, anxiety, mental health disorders, and medications. Treatments include finding the cause, improving sleep patterns, using behavioral therapy, and taking sleeping pills in most cases. However, the drugs often cause worse side effects than insomnia. This study compared the efficacy of initial agomelatine and clonazepam doses with cognitive behavioral therapy for insomnia (CBT-i) in moderate to severe insomnia patients.

Methods

This quasi-experiment study involved 230 moderate to severe insomnia patients with group A as clonazepam 0.25 mg and B as agomelatine 25 mg. CBT-i was received by both of the groups and the Insomnia Severity Index (ISI), Subjective Units of Distress Scale (SUDS) score, medication adherence, and Adverse Drug Reactions (ADRs) were followed for up to 24 weeks.

Results

In the comparative analysis between and within groups, group B exhibited a significant reduction in ISI (p = 0.001) and SUDS (p = 0.001) scores at week 24 compared to group A. Overall, both groups demonstrated improved adherence. However, 12 patients in group A and 10 in group B experienced ADR, which included drowsiness, hypersalivation, diarrhea, maculopapular rash, and myotoxicity. The clonazepam-treated group showed reduced efficacy from week 12 onwards in the ISI and from week 16 in the SUDS median score, which was not observed in the agomelatine group.

Conclusion

The initial dose of agomelatine with CBT-i has a better impact on improving moderate to severe insomnia than the initial dose of clonazepam with CBT-i.

背景：失眠可由多种因素引起，包括睡眠不足、压力、悲伤、荷尔蒙变化、过量咖啡因、焦虑、精神健康障碍和药物。治疗方法包括寻找原因，改善睡眠模式，使用行为疗法，在大多数情况下服用安眠药。然而，这些药物的副作用往往比失眠更严重。本研究比较了阿戈美拉汀和氯硝西泮初始剂量与认知行为治疗失眠（CBT-i）对中重度失眠患者的疗效。方法：对230例中重度失眠症患者进行准实验研究，A组给氯硝西泮0.25 mg， B组给阿戈美拉汀25 mg。两组都接受了CBT-i，并对失眠严重指数（ISI）、主观痛苦量表（SUDS）评分、药物依从性和药物不良反应（adr）进行了长达24 周的随访。结果：在组间和组内的比较分析中，与a组相比，B组在第24周ISI （p = 0.001）和SUDS （p = 0.001）评分显著降低。A组12例，B组10例出现不良反应，包括嗜睡、多涎、腹泻、斑疹、肌毒性等。氯硝西泮治疗组从第12周开始ISI的疗效下降，从第16周开始SUDS中位评分下降，而阿戈美拉汀组没有观察到这一点。结论：阿戈美拉汀联合CBT-i初始剂量对中重度失眠症的改善效果优于氯硝西泮联合CBT-i初始剂量。

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引用次数: 0

Psychostimulant induced behavioral sensitization: The contribution of drug stimuli to context and Pavlovian conditioned stimuli 精神兴奋剂诱导的行为敏感化：药物刺激对情境和巴甫洛夫条件刺激的贡献。

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-06-01 Epub Date: 2025-04-04 DOI: 10.1016/j.pbb.2025.174011

Robert J. Carey

The drug induced enhancement of behavioral stimulation effects with repeated drug treatments is frequently context specific implicating associative processes. Attempts to label these effects as Pavlovian conditioned drug responses have generally been dismissed as it has frequently been demonstrated that the test environment cues alone are insufficient to elicit the sensitized drug response. In this paper evidence will be presented showing that the sensitized drug response can in fact be elicited by test environment cues in a non-drug test. The key reason test environment cues alone are an inadequate conditioned stimulus to elicit the sensitized drug response with commonly used behavioral sensitization protocols is because drug stimulus cues of the drug used to induce behavioral sensitization are conflated with the test environment cues so that the conditioned stimulus has been transformed into a compound conditioned stimulus comprised of the test environment cues co-mingled with the drug stimulus cues In this paper we will present evidence that shows that modifications in the drug testing protocol such as placement of the subject into the test environment immediately after drug administration so that the test environment cues precede the onset of the drug response creates the opportunity for a Pavlovian test environment/drug response association. Also, the use of posttest drug administration can enable the test environment stimulus trace to be selectively paired with the drug response and acquire conditioned stimulus properties and become sufficient to elicit the sensitized behavioral drug response. From a Pavlovian conditioning perspective, repeated pairing of the drug with the test environment enables the conditioned drug response test response to add to the unconditioned drug response to generate a behavioral sensitization effect. Critically, the context needs to be recognized as a conditioned stimulus composite comprised of the test environment cues coupled with the drug generated stimulus cues.

在反复用药的情况下，药物会增强行为刺激效应，这种效应往往与特定的环境有关，牵涉到联想过程。将这些效应称为巴甫洛夫条件性药物反应的尝试一般都会被否定，因为经常有证据表明，仅凭试验环境线索不足以诱发敏化药物反应。本文将提供证据表明，在非药物测试中，测试环境线索实际上可以诱发敏化药物反应。在常用的行为致敏方案中，单靠试验环境线索不足以诱发致敏药物反应，其关键原因是用于诱发行为致敏的药物刺激线索与试验环境线索混淆在一起，从而使条件刺激变成了由试验环境线索与药物刺激线索共同组成的复合条件刺激。在本文中，我们将提出证据，证明对药物测试方案的修改，如在给药后立即将受试者置于测试环境中，使测试环境线索先于药物反应出现，从而为巴甫洛夫测试环境/药物反应关联创造了机会。此外，使用试验后给药可以使试验环境刺激痕迹与药物反应有选择地配对，获得条件刺激特性，并足以引起敏感的行为药物反应。从巴甫洛夫条件反射的角度来看，反复将药物与测试环境配对，可使条件性药物反应测试反应与非条件性药物反应相加，从而产生行为敏化效应。至关重要的是，需要将环境视为一种条件刺激复合体，由试验环境线索和药物产生的刺激线索组成。

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引用次数: 0

Systematic review and meta-analysis of weight gain and metabolic changes in children and adolescents using second-generation antipsychotics 使用第二代抗精神病药物的儿童和青少年体重增加和新陈代谢变化的系统回顾和荟萃分析。

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-06-01 Epub Date: 2025-04-01 DOI: 10.1016/j.pbb.2025.174012

Suzana Figueiredo Collares , Antônio Márcio de Ávila Júnior , Tamires Coelho Martins , Victhor Hugo Martins Rezende , Marco Aurélio Romano-Silva , Renata Maria Silva Santos , Débora Marques de Miranda

The use of second-generation antipsychotics in children and adolescents has significantly increased in recent decades, raising concerns about side effects such as weight gain, dyslipidemia, and insulin resistance. These effects are concerning during development, as they may predispose individuals to adult obesity and metabolic complications. Therefore, the aim of this review is to update the evidence on associations between the use of these medications, weight gain, BMI changes, and major metabolic alterations in children and adolescents. This review was conducted following the PRISMA protocol and registered in PROSPERO under the number: CRD42024549448. The search was carried out in March 2024 using the terms “child,” “adolescent,” “weight gain,” “metabolism disorders,” and “antipsychotics,” combined with the AND operator in the MEDLINE, Scopus, Cochrane, and PubMed databases. The main findings of this review included weight gain, increased BMI, and metabolic alterations, such as insulin resistance and increased abdominal circumference. The meta-analysis highlighted a positive association between one of the investigated second-generation antipsychotics and weight gain. Therefore, prescriptions may be accompanied by strict guidelines for nutritional monitoring and metabolic control interventions.

近几十年来，儿童和青少年中第二代抗精神病药物的使用显著增加，引起了对诸如体重增加、血脂异常和胰岛素抵抗等副作用的关注。这些影响在发育过程中引起关注，因为它们可能使个体易患成人肥胖和代谢并发症。因此，本综述的目的是更新儿童和青少年使用这些药物、体重增加、BMI变化和主要代谢改变之间关联的证据。本综述按照PRISMA方案进行，并在PROSPERO注册，编号：CRD42024549448。搜索于2024年3月进行，使用术语“儿童”、“青少年”、“体重增加”、“代谢紊乱”和“抗精神病药物”，并结合MEDLINE、Scopus、Cochrane和PubMed数据库中的and运算符。这篇综述的主要发现包括体重增加、BMI增加和代谢改变，如胰岛素抵抗和腹围增加。荟萃分析强调了研究的第二代抗精神病药物之一与体重增加之间的正相关。因此，处方可能伴随着严格的营养监测和代谢控制干预指南。

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引用次数: 0

Monoamine receptors targeted by methamphetamine differentially modulate basal and fentanyl-depressed respiration in mice 甲基苯丙胺靶向单胺受体差异调节小鼠基础呼吸和芬太尼抑制呼吸

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-06-01 Epub Date: 2025-03-28 DOI: 10.1016/j.pbb.2025.174004

Harrison J. Elder , D. Matthew Walentiny , Patrick M. Beardsley

Rationale

Fentanyl remains the primary cause of fatal overdoses, and its co-use with methamphetamine is a growing concern. Our lab previously demonstrated that racemic methamphetamine could have either respiratory stimulant or depressant effects depending on dose and separately determined by its enantiomers, dextromethamphetamine, and levomethamphetamine, respectively. Enantiomeric separation of methamphetamine's stimulant and depressant effects indicates that differences in their pharmacology might be exploited to develop novel respiratory stimulants. It is presently unknown which of methamphetamine's monoamine receptor mechanisms mediate these respiratory effects. Thus, systematic evaluation of monoamine receptor-selective agents may identify treatment targets for OIRD.

Methods

Six selective agonists at monoamine receptors involved in methamphetamine's activity [phenylephrine (PNE; α₁), clonidine (CLON; α₂), SKF-82958 (SKF; D₁), quinpirole (QPR; D₂-like), 8-OH-DPAT (8-OH; 5HT_1A), and DOI (5HT₂)] were tested in adult male mice to determine their effects on basal and fentanyl-depressed minute volume (MVb; i.e., respiratory frequency x tidal volume) using whole-body plethysmography. Agonists were initially tested at three behaviorally active doses for their effects on basal MVb. Agonists that stimulated respiration or did not decrease respiration were then tested in combination with fentanyl.

Results

The α₁ and D₁ agonists PNE and SKF dose-dependently increased basal MVb while the α₂ and D₂-like agonists CLON and QPR depressed basal MVb. Neither serotonin receptor agonist significantly altered basal MVb. Under fentanyl-depressed conditions, SKF produced transient but significant increases in MVb, while PNE more persistently elevated it. Interestingly, DOI transiently elevated depressed MVb, while 8-OH further exacerbated OIRD.

Conclusions

Selective activation of monoamine receptors alters basal respiration and OIRD, with D₁ and α₁ receptors representing potential targets as respiratory stimulants, whereas α₂, D₂-like, and 5HT_1A receptors may mediate the exacerbation of OIRD by methamphetamine.

芬太尼仍然是致命过量的主要原因，它与甲基苯丙胺的共同使用日益引起人们的关注。我们的实验室先前证明，外消旋甲基苯丙胺可能具有呼吸刺激或抑制作用，这取决于剂量，并分别由其对映体，右甲基安非他明和左甲基安非他明决定。甲基苯丙胺的兴奋和抑制作用的对映体分离表明，它们在药理学上的差异可能被用来开发新的呼吸兴奋剂。目前尚不清楚甲基苯丙胺的单胺受体机制介导这些呼吸作用。因此，系统评价单胺受体选择性药物可以确定OIRD的治疗靶点。方法六种选择性激动剂参与甲基苯丙胺活性的单胺受体[phenylephrine (PNE；α1)，可乐定(CLON；α2), skf -82958 (skf；D1)，喹匹罗(QPR；d2样),8-OH- dpat (8-OH；5HT1A)和DOI (5HT2)]在成年雄性小鼠中进行检测，以确定它们对基础和芬太尼抑制分钟体积(MVb；即呼吸频率x潮气量)使用全身容积描记术。激动剂最初以三种行为活性剂量测试其对基础MVb的影响。刺激呼吸或不减少呼吸的激动剂随后与芬太尼联合试验。结果α1和D1受体激动剂PNE和SKF呈剂量依赖性增加基础MVb， α2和d2受体激动剂CLON和QPR呈剂量依赖性降低基础MVb。两种5 -羟色胺受体激动剂均未显著改变基础MVb。在芬太尼抑制条件下，SKF产生短暂但显著的MVb升高，而PNE更持久地升高MVb。有趣的是，DOI会短暂升高抑郁的MVb，而8-OH会进一步加重OIRD。结论单胺受体的选择性激活改变了基础呼吸和OIRD，其中D1和α1受体作为呼吸刺激的潜在靶点，而α2、d2样受体和5HT1A受体可能介导甲基苯丙胺对OIRD的加重。

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引用次数: 0