Pharmacology Biochemistry and Behavior最新文献_第7页

Novel insights into kappa and delta opioid receptor function across systems and disorders. Introduction to the special issue 新见解kappa和三角洲阿片受体功能跨系统和疾病。特刊简介

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-09-01 Epub Date: 2025-07-02 DOI: 10.1016/j.pbb.2025.174058

Sari Izenwasser

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 : 2025-09-01 Epub 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

KOR agonists for the treatment and/or prevention of opioid use disorder and cocaine use disorder 治疗和/或预防阿片类药物使用障碍和可卡因使用障碍的KOR激动剂。

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-09-01 Epub Date: 2025-06-28 DOI: 10.1016/j.pbb.2025.174056

Lee-Yuan Liu-Chen, Peng Huang

Reports in the 1990s and 2000s showed that kappa opioid receptor (KOR) agonists might be promising for treatment and/or prevention of opioid use disorder (OUD) and cocaine use disorder (CUD). However, the side effects associated with KOR agonists available at the time, such as psychotomimesis, dysphoria and sedation, prevented clinical development. Subsequently, nalfurafine and recently triazole 1.1 and oxa-noribogaine, three centrally acting KOR agonists devoid of such side effects, have been studied in animal models of OUD and CUD. By and large, earlier findings with typical KOR agonists were replicated with nalfurafine and in limited studies with triazole 1.1 and oxa-noribogaine. KOR agonists reduced reinforcing effects of mu opioid receptor (MOR) agonists and decreased tolerance to and dependence on MOR agonists. Oxa-noribogaine suppressed cue-induced reinstatement of morphine and fentanyl seeking. KOR agonists countered itch elicited by MOR agonists and produced additive analgesic effects with MOR agonists, thus allowing use of lower doses of MOR and KOR agonists, resulting in lower degrees of MOR-related side effects (such as respiratory depression) and typical KOR-associated side effects. In addition, KOR agonists attenuated locomotor sensitization and conditioned place preference sensitization following repeated cocaine, reduced acquisition and maintenance of cocaine self-administration and decreased cocaine-induced increase in extracellular dopamine. KOR agonists also suppressed cocaine priming-induced reinstatement of cocaine seeking. Therefore, a combination of a KOR agonist and a MOR agonist or a compound with dual KOR/MOR agonist activities when used as analgesics will deter escalation use of MOR agonists, thus prevent OUD, and KOR agonists may be useful for treatment of cocaine abuse and relapse. Importantly, KOR agonists with no or fewer side effects of typical KOR agonists should be further investigated in animal models of OUD and CUD, particularly those that simulate stress-, cue- and drug priming-induced relapse for potential clinical development.

20世纪90年代和21世纪初的报告显示，kappa阿片受体（KOR）激动剂可能有望治疗和/或预防阿片使用障碍（OUD）和可卡因使用障碍（CUD）。然而，与当时可用的KOR激动剂相关的副作用，如精神错乱、烦躁不安和镇静，阻碍了临床发展。随后，在OUD和CUD的动物模型中研究了纳氟萘芬和最近的三唑1.1和oxa-noribogaine这三种没有此类副作用的中枢作用KOR激动剂。总的来说，早期关于典型KOR激动剂的研究结果在纳氟芬和有限的三唑1.1和奥沙-去甲bogaine的研究中得到了重复。KOR激动剂降低了mu阿片受体（MOR）激动剂的强化作用，降低了对MOR激动剂的耐受性和依赖性。Oxa-noribogaine抑制线索诱导的吗啡和芬太尼寻找恢复。KOR激动剂对抗MOR激动剂引起的瘙痒，并与MOR激动剂产生附加镇痛作用，从而允许使用较低剂量的MOR和KOR激动剂，导致较低程度的MOR相关副作用（如呼吸抑制）和典型的KOR相关副作用。此外，KOR激动剂可减弱反复使用可卡因后的运动致敏和条件性位置偏好致敏，减少可卡因自我给药的获得和维持，减少可卡因诱导的细胞外多巴胺的增加。KOR激动剂也抑制可卡因启动诱导的可卡因寻找的恢复。因此，将KOR激动剂和MOR激动剂联合使用或将具有双重KOR/MOR激动剂活性的化合物用作镇痛药时，将阻止MOR激动剂的使用升级，从而预防OUD，并且KOR激动剂可能对治疗可卡因滥用和复发有用。重要的是，与典型的KOR激动剂相比，没有或更少副作用的KOR激动剂应该在OUD和CUD的动物模型中进一步研究，特别是那些模拟应激、线索和药物启动诱导的复发的药物，以进行潜在的临床开发。

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引用次数: 0

Chronic modulation of endocannabinoid receptors does not impact hyperactivity, risk behavior, and working memory in an animal model of attention-deficit/hyperactivity disorder 在注意缺陷/多动障碍动物模型中，内源性大麻素受体的慢性调节不会影响多动、危险行为和工作记忆

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-09-01 Epub Date: 2025-07-04 DOI: 10.1016/j.pbb.2025.174059

Daniel Bussinger de Souza Penna , Samara Gumiéro Costa , Marina Pollis Davis , Karin da Costa Calaza , Alexandre dos Santos Rodrigues , Pablo Pandolfo

Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder characterized by impairments in executive functions, including behavioral inhibition and working memory. The most widely accepted neurobiological explanation for ADHD is related to dopaminergic hypofunction. The dopaminergic system is modulated by endocannabinoid ligands, primarily through the action of cannabinoid receptors type 1 and 2 (CB1R and CB2R) within frontostriatal circuits. Spontaneously hypertensive rats (SHR) are a widely used animal model for studying the neurobiology of ADHD. Our recent study demonstrated that acute treatment with synthetic CB1R and CB2R ligands increased hyperactivity and risk-taking behavior in SHR. We now investigate how chronic modulation of these receptors affects hyperactivity, risk-taking behavior, and working memory assessment in SHR. As expected, the SHR exhibited hyperactivity, difficulties in risk assessment, impaired working memory, and increased risk-taking behavior. Notably, females SHR displayed higher levels of locomotion and risk-taking behavior than their male counterparts, regardless of treatment. Chronic modulation of CB1R and CB2R did not lead to significant changes in any of the evaluated behavioral parameters. Further research is needed to understand both the acute and chronic effects of manipulating cannabinoid receptors and endocannabinoids in the context of ADHD.

注意缺陷/多动障碍（ADHD）是一种以执行功能受损为特征的神经发育障碍，包括行为抑制和工作记忆。ADHD最被广泛接受的神经生物学解释与多巴胺能功能减退有关。多巴胺能系统由内源性大麻素配体调节，主要通过大麻素受体1型和2型（CB1R和CB2R）在额纹状体回路中的作用。自发性高血压大鼠（SHR）是一种广泛应用于ADHD神经生物学研究的动物模型。我们最近的研究表明，用合成CB1R和CB2R配体进行急性治疗会增加SHR患者的多动和冒险行为。我们现在研究这些受体的慢性调节如何影响SHR的多动、冒险行为和工作记忆评估。正如预期的那样，SHR表现出多动症、风险评估困难、工作记忆受损和冒险行为增加。值得注意的是，无论治疗方式如何，女性SHR表现出比男性更高的运动水平和冒险行为。CB1R和CB2R的慢性调节并未导致任何被评估行为参数的显著变化。需要进一步的研究来了解在ADHD背景下操纵大麻素受体和内源性大麻素的急性和慢性影响。

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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 : 2025-09-01 Epub 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

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 : 2025-09-01 Epub 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

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 : 2025-09-01 Epub 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

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 : 2025-08-01 Epub 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 : 2025-08-01 Epub 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 : 2025-08-01 Epub 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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