Pharmacology Biochemistry and Behavior最新文献_第9页

Schizophrenia-like phenotypes and long-term synaptic plasticity impairment in GluN2A-transgenic mice glun2a转基因小鼠的精神分裂症样表型和长期突触可塑性损伤

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-04-29 DOI: 10.1016/j.pbb.2025.174026

Huan Zhang , Wen Si , Bo Wang , Jiao Han , Fan Ding , Qingsheng Xue , Xiaohua Cao

While N-methyl-d-aspartate receptor (NMDAR) hypofunction has been suggested as a hallmark of schizophrenia, the role of subunit-specific dysregulation such as GluN2A overexpression remains poorly understood. The present study comprehensively investigated the impact of GluN2A overexpression on behavioral phenotypes, cognitive functions, and synaptic plasticity in transgenic mice with forebrain-specific overexpression of the GluN2A subunit (GluN2A-TG). Behavioral assessments revealed schizophrenia-like phenotypes, including prolonged stereotypic movement duration, impaired sensorimotor gating, reduced social interaction, and diminished nest-building activity in GluN2A-TG mice. Consistently, GluN2A-TG mice exhibited not only deficits in spatial working memory and olfactory working memory but also impaired associative learning. In addition, both long-term potentiation and long-term depression were significantly attenuated in the prefrontal cortex (PFC) of GluN2A-TG mice. Furthermore, electrophysiological analysis of NMDAR-mediated excitatory postsynaptic currents in PFC neurons revealed altered kinetics characterized by a faster decay time and significantly increased amplitude in GluN2A-TG mice. Collectively, these findings suggest that GluN2A overexpression may induce schizophrenia-like phenotypes via impairing NMDAR-dependent long-term synaptic plasticity in the PFC, likely due to altered NMDAR subunit composition leading to disrupted calcium signaling dynamics. These results provide critical insights into the pathological role of GluN2A in schizophrenia.

虽然n -甲基-d-天冬氨酸受体（NMDAR）功能低下已被认为是精神分裂症的一个标志，但亚单位特异性失调（如GluN2A过表达）的作用仍然知之甚少。本研究全面研究了GluN2A过表达对GluN2A亚基（GluN2A- tg）前脑特异性过表达转基因小鼠行为表型、认知功能和突触可塑性的影响。行为评估显示GluN2A-TG小鼠具有精神分裂症样表型，包括刻板印象运动持续时间延长、感觉运动门控受损、社交互动减少和筑巢活动减少。GluN2A-TG小鼠不仅表现出空间工作记忆和嗅觉工作记忆的缺陷，而且还表现出联想学习的障碍。此外，GluN2A-TG小鼠前额皮质（PFC）的长期增强和长期抑郁均显著减弱。此外，对nmdar介导的PFC神经元突触后兴奋性电流的电生理分析显示，GluN2A-TG小鼠的动力学发生了改变，其特征是衰减时间更快，振幅显著增加。总的来说，这些发现表明GluN2A过表达可能通过损害PFC中NMDAR依赖的长期突触可塑性来诱导精神分裂症样表型，可能是由于NMDAR亚基组成的改变导致钙信号动力学被破坏。这些结果为GluN2A在精神分裂症中的病理作用提供了重要的见解。

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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 : 2025-04-23 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

Drosophila model of depression-like behavior: systematic investigation of external stress parameters and intrinsic susceptibility 果蝇抑郁样行为模型：外部应激参数和内在易感性的系统研究

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-04-20 DOI: 10.1016/j.pbb.2025.174014

Wenhao Zhang , Zhifu Ai , Genhua Zhu , Ming Yang , Yali Liu , Huanhua Xu , Qin Zheng , Yonggui Song , Dan Su

Currently, Drosophila is widely used to study brain diseases. Unfortunately, Drosophila still lacks a mature and stable model for research on depression. This study addressed this issue by systematically exploring external stress and intrinsic susceptibility factors (Drosophila strains, adult/larval forms) that may influence the establishment and reproducibility of the stress-induced model. On this basis, the parameters are optimized. The results indicate Drosophila strains and forms are critical factors influencing model establishment, while external stress is the primary cause affecting the model's mortality rate. Compared with the other four strains, Canton-S are the most susceptible to chronic unpredictable mild stress (CUMS). Larval forms exhibit lower reactivity to external stress compared to adults. Parameter variations greatly influence model mortality rates from cold/heat/starvation stress. The model methodology validation study conducted subsequently through assessments of face, construct, and predictive validity demonstrates that the model exhibits face (neurobehavioral differences), structural (neurotransmitter changes in the Drosophila brain), and predictive (behavioral changes after fluoxetine treatment) validity. Additionally, spatial behavior experiments in Drosophila provide more realistic activity patterns compared to planar behavior, minimizing potential errors in interpreting lateral movements of the Drosophila, and it is recommended that this metric be included in model evaluation. This study presents a comprehensive set of methods for establishing and evaluating a depression-like behavior model and offers greater convenience for research on the pathogenesis of depression, as well as the screening, efficacy evaluation, and mechanistic studies of antidepressant drugs.

目前，果蝇被广泛用于研究脑部疾病。遗憾的是，果蝇仍然缺乏一个成熟稳定的抑郁症研究模型。本研究针对这一问题，系统探讨了可能影响应激诱导模型建立和可重复性的外部应激和内在易感因素（果蝇品系、成虫/幼虫形态）。在此基础上，对参数进行了优化。结果表明，果蝇品系和形态是影响模型建立的关键因素，而外部应激则是影响模型死亡率的主要原因。与其他四个品系相比，Canton-S最容易受到慢性不可预知温和应激（CUMS）的影响。与成虫相比，幼虫对外界压力的反应能力较低。参数变化在很大程度上影响了冷/热/饥饿应激的模型死亡率。随后通过面效、结构效和预测效评估进行的模型方法验证研究表明，该模型具有面效（神经行为差异）、结构效（果蝇大脑中神经递质的变化）和预测效（氟西汀治疗后的行为变化）。此外，与平面行为相比，果蝇的空间行为实验能提供更真实的活动模式，最大限度地减少解读果蝇横向运动时可能出现的误差，因此建议将这一指标纳入模型评估。本研究提出了一套建立和评估抑郁样行为模型的综合方法，为抑郁症发病机制的研究以及抗抑郁药物的筛选、疗效评估和机理研究提供了更大的便利。

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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 : 2025-04-18 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

Pre-exposure to eutylone attenuates its own aversive effects but has no impact on cocaine or MDMA: A possible role of eutylone's hybrid pharmacology 预暴露于真tylone减弱其自身的不良影响，但对可卡因或MDMA没有影响：真tylone的混合药理学的可能作用

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-04-17 DOI: 10.1016/j.pbb.2025.174013

Negar G. Ardabili, Shira Tan, Anthony L. Riley

Previous research has reported that pre-exposure to a variety of drugs of abuse can impact (reduce) the aversive effects of themselves and other abused compounds, often as a function of their shared pharmacological activity. In this context, the present series of studies investigated the effects of history with the synthetic cathinone eutylone on the aversive effects of cocaine, MDMA, and itself in adult, male Sprague-Dawley rats. Given eutylone's structural similarities with its parent compound methylone, it was predicted that its ability to attenuate cocaine- and MDMA-induced taste avoidance would parallel the effects of methylone pre-exposure in this design (cocaine > MDMA). In Experiment 1, male Sprague-Dawley rats were exposed to eutylone (20 mg/kg, IP) or equivolume saline every other day for five exposures followed by taste avoidance conditioning with 20 mg/kg cocaine (SC) or 1.8 mg/kg MDMA (SC). Both cocaine and MDMA induced significant taste avoidance that developed over repeated conditioning trials. Cocaine and MDMA-induced avoidance were unaffected by eutylone history. To assess the general ability of eutylone pre-exposure to attenuate taste avoidance conditioning in the pre-exposure design, in Experiment 2, an additional set of male Sprague-Dawley rats was injected with 20 mg/kg eutylone (IP) prior to taste avoidance conditioning with eutylone (20 mg/kg (IP). Under these conditions, eutylone-induced avoidance was attenuated by eutylone pre-exposure. Given that eutylone history attenuated eutylone-induced avoidance argues that the failure to affect cocaine or MDMA was not a function of eutylone in this preparation. The inability of eutylone to attenuate the aversive effects of cocaine and MDMA despite sharing pharmacological activity suggests that eutylone's hybrid pharmacology may create a unique interoceptive effect different than that produced by either drug.

以往的研究表明，预先接触各种滥用药物会影响（降低）其本身和其他滥用化合物的厌恶效应，这通常是由于它们具有共同的药理活性。在这种情况下，本系列研究调查了在成年雄性 Sprague-Dawley 大鼠体内使用合成卡西酮优泰酮对可卡因、摇头丸和自身的厌恶效应的影响。鉴于丁酮与其母体化合物甲酮在结构上的相似性，我们预测丁酮减弱可卡因和亚甲二氧基甲基苯丙胺诱发的味觉回避的能力将与本设计（可卡因> 亚甲二氧基甲基苯丙胺）中预先暴露甲酮的效果相似。在实验 1 中，雄性 Sprague-Dawley 大鼠每隔一天暴露于优甲龙（20 毫克/千克，IP）或等体积生理盐水，共暴露 5 次，然后用 20 毫克/千克可卡因（SC）或 1.8 毫克/千克摇头丸（SC）进行味觉回避调节。可卡因和亚甲二氧基甲基苯丙胺都会诱发明显的味觉回避，这种回避会在重复的条件反射试验中逐渐形成。可卡因和亚甲二氧基甲基苯丙胺诱导的回避不受优甲乐的影响。在实验 2 中，为了评估在预暴露设计中丁酮预暴露减弱味觉回避条件反射的一般能力，在用丁酮（20 毫克/千克（IP））进行味觉回避条件反射之前，又给一组雄性 Sprague-Dawley 大鼠注射了 20 毫克/千克丁酮（IP）。在这些条件下，丁酮诱导的回避会因预先暴露于丁酮而减弱。鉴于戊乙酮会减弱戊乙酮诱导的回避，这就表明在这种制剂中，戊乙酮对可卡因或亚甲二氧基甲基苯丙胺没有影响并不是它的作用。尽管具有相同的药理活性，但丁乙酮无法减弱可卡因和摇头丸的厌恶效应，这表明丁乙酮的混合药理作用可能会产生不同于这两种药物的独特感知间效应。

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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 : 2025-04-04 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 : 2025-04-01 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 : 2025-03-28 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

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 : 2025-03-27 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

Dopamine type II receptors in amygdala along with oxytocin in hypothalamus regulate social behavior in male mandarin voles 雄性田鼠杏仁核中的多巴胺II型受体和下丘脑中的催产素共同调节着雄性田鼠的社会行为

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-03-24 DOI: 10.1016/j.pbb.2025.174002

Xiaolei An , Peng Yu , Gang Chang

The amygdala dopamine (DA) system and hypothalamic oxytocin (OT) play important roles in emotion regulation, and emotions are important in regulating social behavior. However, it is unclear whether DA in the amygdala is involved in the regulation of social behavior, and whether OT in the hypothalamus is also involved in this process. In this study, we examined the release of DA in the medial amygdala (MeA) during different social interactions and the effect of injecting the dopamine II receptor (D2R) agonist quinpirole and the D2R antagonist raclopride into the MeA on social behavior and OT in the paraventricular nucleus (PVN) and supraoptic nucleus (SON), as well as in the blood of male mandarin voles (Microtus mandarinus). The results showed that the DA in the MeA increased in the process of social behavior, and the DA in the face of strangers was higher than that in the face of familiars. In addition, the injection of D2R antagonists in the MeA reduced attacking and escaping behaviors but increased physical contact and investigating behaviors, increased the number of OT-IR neurons in the PVN and SON, and increased OT levels in the blood. While injection of D2R agonists in the MeA increased attacking and escaping behaviors but reduced physical contact and investigating behaviors, it also reduced OT-IR neurons in the SON. In conclusion, D2R in the medial amygdala and oxytocin in the hypothalamus regulate social behavior.

杏仁核多巴胺（DA）系统和下丘脑催产素（OT）在情绪调节中起重要作用，情绪在调节社会行为中起重要作用。然而，杏仁核中的DA是否参与社会行为的调节，以及下丘脑中的OT是否也参与这一过程，目前尚不清楚。在这项研究中，我们检测了不同社会交往时多巴胺在内侧杏仁核（MeA）的释放，以及在内侧杏仁核注射多巴胺II受体（D2R）激动剂quinpirole和D2R拮抗剂raclopride对雄性田鼠（Microtus mandarinus）室旁核（PVN）和视上核（SON）以及血液中社交行为和OT的影响。结果表明，MeA中的DA在社交行为过程中有所增加，面对陌生人时的DA高于面对熟悉者时的DA。此外，在MeA中注射D2R拮抗剂减少了攻击和逃避行为，但增加了身体接触和调查行为，增加了PVN和SON中OT- ir神经元的数量，并增加了血液中的OT水平。虽然在MeA中注射D2R激动剂增加了攻击和逃避行为，但减少了身体接触和调查行为，但它也减少了SON中的OT-IR神经元。综上所述，内侧杏仁核的D2R和下丘脑的催产素调节着社会行为。

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引用次数: 0