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Intermittent environmental enrichment induces behavioral despair, while intermittent social isolation impairs spatial learning in rats 间歇性的环境丰富会导致行为绝望,而间歇性的社会隔离则会损害大鼠的空间学习能力。
IF 3.3 3区 心理学 Q1 BEHAVIORAL SCIENCES Pub Date : 2025-03-19 DOI: 10.1016/j.pbb.2025.174001
Aybuke Akkaya , Deren Aykan , Sinem Gencturk, Gunes Unal
Environmental enrichment and social isolation constitute two well-studied experimental manipulations that result in several behavioral, neural, and molecular changes in rodents. Enrichment is linked to enhanced cognitive performance, and mitigation of different nervous system injuries and disorders. In contrast, social isolation or impoverished environment often induce negative effects on cognitive and affective systems. Both manipulations are typically examined with a short-term or chronic exposure, which cannot capture the actual human experiences. In this study, we explored the behavioral and neural alterations led by intermittent environmental enrichment or social isolation in adult Wistar rats. Animals were assigned to an enriched condition (EC), isolation/impoverished condition (IC), or standard condition (SC). The differential housing protocol involved transferring the animals to their respective cages for two days at the end of each five-day standard housing period for 8 weeks. Enriched animals exhibited behavioral despair in the forced swim test without differential overall locomotor activity. In the Morris water maze, impoverished animals displayed a slower learning rate compared to the SC and EC groups. In line with this, the IC group had fewer parvalbumin (PV) immunopositive (+) cells in the CA1 and dentate gyrus. No differences were observed in PV+ cell levels in the amygdala, while the IC group had more c-Fos+ cells in the same region following acute restraint stress. These findings implicate that intermittent isolation or enrichment are sufficient to trigger distinct behavioral changes at the cognitive and affective domains, and pinpoint PV as a biomarker for environmentally induced alterations in hippocampal memory performance.
环境丰富和社会隔离构成了两种被充分研究的实验操作,它们会导致啮齿动物的一些行为、神经和分子变化。浓缩与增强认知能力和减轻不同神经系统损伤和疾病有关。相反,社会孤立或贫困的环境往往会对认知和情感系统产生负面影响。这两种操作通常都是通过短期或长期暴露来检查的,这无法捕捉到实际的人类体验。在这项研究中,我们探讨了成年Wistar大鼠在间歇性环境丰富或社会隔离下的行为和神经改变。动物被分配到丰富条件(EC),隔离/贫困条件(IC)和标准条件(SC)。差别饲养方案涉及在8 周的每个5天标准饲养期结束时将动物转移到各自的笼子中,为期两天。富营养化动物在强迫游泳试验中表现出行为绝望,整体运动活动无差异。在莫里斯水迷宫中,贫困动物的学习速度比SC组和EC组慢。与此一致,IC组CA1和齿状回的小白蛋白(PV)免疫阳性(+)细胞较少。在杏仁核的PV+细胞水平没有观察到差异,而IC组在急性约束应激后同一区域有更多的c-Fos+细胞。这些发现表明,间歇性分离或富集足以引发认知和情感领域的明显行为变化,并指出PV是环境诱导海马记忆性能改变的生物标志物。
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引用次数: 0
Operant effort-based decision-making task reveals sex differences in motivational behavior but no long-term effects of adolescent intermittent ethanol in Sprague Dawley rats 操作性努力决策任务揭示了青春期间歇乙醇对Sprague Dawley大鼠动机行为的性别差异,但没有长期影响
IF 3.3 3区 心理学 Q1 BEHAVIORAL SCIENCES Pub Date : 2025-03-17 DOI: 10.1016/j.pbb.2025.173998
Anny Gano, Andrew S. Vore, Daniella Geraci, Elena I. Varlinskaya, Terrence Deak
Loss of motivated behavior, or apathy, is a key feature across multiple affective disorders, and is assessed via operant effort-based decision-making (EBDM). The mechanisms of amotivation have been connected to pro-inflammatory signaling which can directly impact dopamine signaling. Chronic alcohol exposure is associated with altered immune signaling and impaired goal-directed behavior, so the present studies assessed the impact of adolescent intermittent ethanol (AIE) on EBDM in adulthood across sex. Adolescent male and female (N = 32/n = 8 per group) Sprague-Dawley rats were exposed to ethanol (4 g/kg) intragastrically on a 3 days on/2 days off schedule during postnatal days ~30–50 or given vehicle, and allowed to age into adulthood (P80+). All rats were then trained on the operant EBDM concurrent FR5/chow task, after which we tested the impact of sex and AIE history on responding 1) during breakpoint challenge raising the FR requirement in a log2 pattern, 2) 90 min after immune challenge (2 μg/kg IL-1β), 3) 18 h after 3.5 g/kg intraperitoneal ethanol challenge (hangover), and 4) immediately after a 30-min restraint stress challenge. Immune challenge disrupted motivated behavior without affecting appetite. No effects of AIE emerged and sex differences were evident throughout all challenges. Females responded less for pellets yet persisted responding until a higher breakpoint. This work indicates that AIE does not alter baseline or evoked EBDM as can be measured with this approach. Testing across aging and using other modalities should be performed to continue examining the effects of chronic alcohol on apathy.
动机行为的丧失,或冷漠,是多种情感障碍的一个关键特征,并通过操作性努力决策(EBDM)进行评估。动机机制与促炎信号直接影响多巴胺信号有关。慢性酒精暴露与免疫信号改变和目标导向行为受损有关,因此本研究评估了青少年间歇性酒精(AIE)对成年期EBDM的影响。在出生后~30 ~ 50天或给药期间,按3天开/停2天的时间,将青春期雄性和雌性sd大鼠(N = 32/ N = 8 /组)灌胃酒精(4 g/kg),直至成年(P80+)。然后对所有大鼠进行操作性EBDM并发FR5/chow任务训练,之后我们测试了性别和AIE史对反应的影响:1)在以log2模式提高FR需求的breakpoint刺激期间,2)免疫刺激(2 μg/kg IL-1β)后90分钟,3)3.5 g/kg腹腔内乙醇刺激(宿醉)后18小时,4)在限制性应激刺激30分钟后立即。免疫挑战破坏了动机行为,但不影响食欲。AIE没有产生任何影响,性别差异在所有挑战中都很明显。雌性对颗粒的反应较少,但持续反应,直到更高的断点。这项工作表明,AIE不会改变基线或诱发EBDM,可以用这种方法测量。应该进行跨年龄和使用其他方式的测试,以继续检查慢性酒精对冷漠的影响。
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引用次数: 0
Co-treatment with cannabidiol and escitalopram in ineffective doses induces antidepressant effect in maternally separated male adolescent rats 无效剂量大麻二酚和艾司西酞普兰共同治疗母分离雄性青春期大鼠的抗抑郁作用。
IF 3.3 3区 心理学 Q1 BEHAVIORAL SCIENCES Pub Date : 2025-03-14 DOI: 10.1016/j.pbb.2025.174000
Jonasz Dragon, Miłosz Gołyszny, Ewa Obuchowicz
Due to low efficacy and delayed therapeutic effect of drugs currently used in the therapy of depression in adolescent population, a lot of effort has been put into finding new substances using alternative target points that could support treatment with traditional antidepressive drugs. Cannabidiol, compound derived from Cannabis sativa may have therapeutic potential in depressive disorders. This study aimed to investigate whether combined administration of escitalopram with cannabidiol in ineffective doses, will provide better or similar effects in behavioral tests compared to escitalopram in an effective dose in adolescent maternally separated rats. Maternal separation has been used as a form of early life adversity. The pups were separated from their dams for 360 min daily from postnatal day (PND) 2 until PND 15. Later, escitalopram (15 or 5 mg/kg) or vehicle were administered ip. in a subacute manner in mid-adolescent male rats. Cannabidiol (15 mg/kg) or vehicle were injected ip. in a single dose about 1 h prior to behavioral assessment. Three standard behavioral tests were performed: the elevated plus maze and the open field test on PND 42 and the forced swimming test on PND 43–44 on the subsequent groups of rats. The combined treatment with escitalopram and cannabidiol in ineffective doses did not induce anxiolytic-like effects but successfully relieved despair behavior in the forced swimming test showing similar efficacy as treatment with escitalopram in effective dose. This result might be the basis for future research and the development of new therapeutic strategies for treatment of adolescent depression.
由于目前用于治疗青少年抑郁症的药物疗效不佳且疗效延迟,人们一直在努力寻找使用替代靶点的新物质,以支持传统抗抑郁药物的治疗。大麻二酚是从大麻中提取的化合物,可能具有治疗抑郁症的潜力。本研究旨在探讨,与有效剂量的艾司西酞普兰相比,以无效剂量联合服用艾司西酞普兰与大麻二酚是否能在青少年母鼠分离的行为测试中提供更好或相似的效果。母鼠分离一直被用作早期生活逆境的一种形式。从出生后第2天到第15天,幼鼠每天与母鼠分离360分钟。之后,以亚急性方式给青春期中期雄性大鼠静脉注射艾司西酞普兰(15 或 5 毫克/千克)或药物。在行为评估前约 1 小时,给大鼠静脉注射一次大麻二酚(15 毫克/千克)或药物。对随后各组大鼠进行了三项标准行为测试:在 PND 42 进行的高架加迷宫和开阔地测试,以及在 PND 43-44 进行的强迫游泳测试。无效剂量的艾司西酞普兰和大麻二酚联合治疗并不能诱导抗焦虑样作用,但却能成功缓解强迫游泳测试中的绝望行为,其疗效与有效剂量的艾司西酞普兰治疗相似。这一结果可作为今后研究和开发治疗青少年抑郁症新策略的基础。
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引用次数: 0
Melanin-concentrating hormone: A promising target for antidepressant treatment 黑色素浓缩激素:抗抑郁治疗的前景光明的靶点
IF 3.3 3区 心理学 Q1 BEHAVIORAL SCIENCES Pub Date : 2025-03-11 DOI: 10.1016/j.pbb.2025.173999
Lingchang Shi , Ying He , Yujun Lian , Jie Luo , Xuan Zhu , Hongqing Zhao
Depression represents a complex neuropsychiatric disorder with an escalating global health burden, characterized by heterogeneous pathophysiology and profound impairments in cognitive-emotional functioning. Current treatment methods have limited efficacy in some individuals and may induce undesirable side effects, necessitating the exploration of novel therapeutic targets and techniques. Emerging research has identified neuropeptide systems as pivotal regulators of mood-related circuits, with melanin-concentrating hormone (MCH) signaling emerging as a particularly promising candidate for antidepressant development. The potential involvement of MCH in the pathophysiology of depression was first proposed over two decades ago. Since then, accumulating evidence from recent studies has progressively illuminated its multifaceted roles in modulating depressive behaviors and underlying neurobiological mechanisms. This review systematically analyzes the mechanistic interplay between MCH signaling and depression pathophenotypes, including its relationship with the hypothalamic-pituitary-adrenal (HPA) axis, neurotransmitter systems, synaptic plasticity, and the regulation of sleep-wakefulness. Particular emphasis is placed on advancing the therapeutic rationale for MCH receptor 1 (MCHR1) antagonists, which demonstrate rapid-onset antidepressant efficacy in preclinical studies compared to traditional agents. Nonetheless, the antidepressant mechanism of the MCH system still requires further elucidation to confirm its therapeutic potential.
抑郁症是一种复杂的神经精神疾病,具有不断升级的全球健康负担,其特征是异质性病理生理和认知情绪功能的严重损害。目前的治疗方法对某些个体的疗效有限,并可能引起不良的副作用,需要探索新的治疗靶点和技术。新兴研究已经确定神经肽系统是情绪相关回路的关键调节因子,其中黑色素浓缩激素(MCH)信号成为抗抑郁药物开发的特别有希望的候选者。MCH在抑郁症病理生理学中的潜在参与是在20多年前首次提出的。从那以后,从最近的研究中积累的证据逐渐阐明了它在调节抑郁行为和潜在的神经生物学机制中的多方面作用。本文系统分析了MCH信号通路与抑郁症病理表型之间的相互作用机制,包括其与下丘脑-垂体-肾上腺(HPA)轴、神经递质系统、突触可塑性和睡眠-觉醒调节的关系。特别强调的是推进MCH受体1 (MCHR1)拮抗剂的治疗原理,在临床前研究中,与传统药物相比,MCHR1拮抗剂显示出快速起效的抗抑郁疗效。尽管如此,MCH系统的抗抑郁机制仍需要进一步阐明以确认其治疗潜力。
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引用次数: 0
Divergent effects of noradrenergic activation and orexin receptor 1 blockade on hippocampal structure, anxiety-like behavior, and social interaction following chronic stress 慢性应激后去甲肾上腺素能激活和食欲素受体1阻断对海马结构、焦虑样行为和社会互动的不同影响
IF 3.3 3区 心理学 Q1 BEHAVIORAL SCIENCES Pub Date : 2025-03-10 DOI: 10.1016/j.pbb.2025.173997
Masoumeh Sarfi, Mahmoud Elahdadi Salmani, Taghi Lashkarbolouki, Iran Goudarzi
Chronic stress (Ch.S) has detrimental effects on the brain's structure and function, particularly in the hippocampus. The noradrenergic and orexinergic systems play crucial roles in the stress response and regulation of stress-related behaviors. This study aimed to investigate the interaction between noradrenergic activation and orexin receptor 1 inhibition on chronic stress-induced hippocampal alterations.
The study conducted experiments on male Wistar rats, subjected to Ch.S, OXr1 blocking, noradrenergic activation, or a combination of these treatments. Plasma corticosterone level was measured using a fluorometric method. Behavioral assessment of social maze, elevated plus maze (EPM) and novel object recognition (NOR) test were performed. Then, the expression of prepro-orexin, OXr1, and glucocorticoid receptor (GR) was analyzed using semiquantitative RT-PCR. Neuronal populations were quantified through Nissl staining.
The data revealed that all stress and yohimbine groups had elevated plasma corticosterone levels. Ch.S significantly altered behavior, impairing social interaction, disrupting object recognition memory and increasing anxiety-like responses in the EPM. OXr1 blocking reversed these stress-induced behavioral deficits, while yohimbine did not improve these behavioral outcomes. Chronic stress led to a significant increase in prepro-orexin, OXr1, and GR expression. While blocking OXr1 helped counteract these stress-induced changes, yohimbine failed to restore the expression levels. Ch.S reduced hippocampal neuronal populations, while OXr1 blocking partially reversed this effect, and yohimbine further recovered the reversal.
These findings indicate that blocking hippocampal OXr1 can mitigate the adverse effects of chronic stress on both hippocampal structure and anxiety-like behaviors, while noradrenergic signaling appears to have differential effects on behavioral and cellular measures.
慢性压力(chs)对大脑的结构和功能,特别是海马体有不利影响。去甲肾上腺素能和增氧能系统在应激反应和应激相关行为的调节中起着至关重要的作用。本研究旨在探讨去甲肾上腺素能激活和食欲素受体1抑制在慢性应激性海马改变中的相互作用。该研究对雄性Wistar大鼠进行了实验,分别进行了chs、OXr1阻断、去甲肾上腺素能激活或这些治疗的组合。采用荧光法测定血浆皮质酮水平。进行社交迷宫、高难度迷宫(EPM)和新目标识别(NOR)测试的行为评估。然后,采用半定量RT-PCR分析pre - pro-orexin、OXr1和糖皮质激素受体(GR)的表达。通过尼氏染色定量神经元群体。数据显示,所有应激组和育亨宾组血浆皮质酮水平均升高。chs显著改变了行为,损害了社会互动,破坏了物体识别记忆,增加了EPM中的焦虑样反应。OXr1阻断逆转了这些应激诱导的行为缺陷,而育亨宾没有改善这些行为结果。慢性应激导致pre - pro-orexin、OXr1和GR表达显著增加。虽然阻断OXr1有助于抵消这些应激引起的变化,育亨宾未能恢复表达水平。Ch.S减少海马神经元数量,而OXr1阻断部分逆转了这种作用,育亨宾进一步恢复了这种逆转。这些发现表明,阻断海马OXr1可以减轻慢性应激对海马结构和焦虑样行为的不利影响,而去甲肾上腺素能信号似乎对行为和细胞措施有不同的影响。
{"title":"Divergent effects of noradrenergic activation and orexin receptor 1 blockade on hippocampal structure, anxiety-like behavior, and social interaction following chronic stress","authors":"Masoumeh Sarfi,&nbsp;Mahmoud Elahdadi Salmani,&nbsp;Taghi Lashkarbolouki,&nbsp;Iran Goudarzi","doi":"10.1016/j.pbb.2025.173997","DOIUrl":"10.1016/j.pbb.2025.173997","url":null,"abstract":"<div><div>Chronic stress (Ch.S) has detrimental effects on the brain's structure and function, particularly in the hippocampus. The noradrenergic and orexinergic systems play crucial roles in the stress response and regulation of stress-related behaviors. This study aimed to investigate the interaction between noradrenergic activation and orexin receptor 1 inhibition on chronic stress-induced hippocampal alterations.</div><div>The study conducted experiments on male Wistar rats, subjected to Ch.S, OXr1 blocking, noradrenergic activation, or a combination of these treatments. Plasma corticosterone level was measured using a fluorometric method. Behavioral assessment of social maze, elevated plus maze (EPM) and novel object recognition (NOR) test were performed. Then, the expression of prepro-orexin, OXr1, and glucocorticoid receptor (GR) was analyzed using semiquantitative RT-PCR. Neuronal populations were quantified through Nissl staining.</div><div>The data revealed that all stress and yohimbine groups had elevated plasma corticosterone levels. Ch.S significantly altered behavior, impairing social interaction, disrupting object recognition memory and increasing anxiety-like responses in the EPM. OXr1 blocking reversed these stress-induced behavioral deficits, while yohimbine did not improve these behavioral outcomes. Chronic stress led to a significant increase in prepro-orexin, OXr1, and GR expression. While blocking OXr1 helped counteract these stress-induced changes, yohimbine failed to restore the expression levels. Ch.S reduced hippocampal neuronal populations, while OXr1 blocking partially reversed this effect, and yohimbine further recovered the reversal.</div><div>These findings indicate that blocking hippocampal OXr1 can mitigate the adverse effects of chronic stress on both hippocampal structure and anxiety-like behaviors, while noradrenergic signaling appears to have differential effects on behavioral and cellular measures.</div></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"250 ","pages":"Article 173997"},"PeriodicalIF":3.3,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143600953","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
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 Pub 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
Coadministration of scopolamine and mGlu2 receptor negative allosteric modulator VU6001966 as a potential therapeutic approach for depression: Rat frontal cortex neurochemistry and behavior 东莨菪碱和mGlu2受体负变构调节剂VU6001966作为抑郁症的潜在治疗方法:大鼠额叶皮质神经化学和行为
IF 3.3 3区 心理学 Q1 BEHAVIORAL SCIENCES Pub Date : 2025-03-07 DOI: 10.1016/j.pbb.2025.173996
Yana Babii , Agnieszka Pałucha-Poniewiera , Krystyna Gołembiowska , Agnieszka Bysiek , Izabela Szpręgiel , Andrzej Pilc
Clinical studies provide evidence that scopolamine, a nonselective antagonist of muscarinic cholinergic receptors, exerts rapid and prolonged antidepressant effects. However, its use as a psychiatric drug has been limited due to its significant adverse effects. A therapeutic option that could help reduce the adverse effects of scopolamine is its coadministration at lower doses with other substances with similar antidepressant properties. To address this issue, we have investigated the effect of a single acute coadministration of scopolamine and a negative allosteric modulator of the mGlu2 receptor VU6001966 on rat behavior using a forced swim test (FST) and locomotor activity test. The effect of given compounds on the extracellular levels of neurotransmitters in the rat frontal cortex (FCX) was examined using microdialysis in freely moving rats. Both scopolamine and VU6001966 induced dose-dependent antidepressant-like effects in the FST test without affecting locomotor activity. Furthermore, VU6001966 enhanced extracellular dopamine and serotonin levels while lowering glutamate, without affecting GABA level. Both scopolamine alone or in combination with VU6001966 increased dopamine, serotonin, and glutamate levels in the FCX, without affecting GABA levels. Our results suggest that coadministration of scopolamine with mGlu2 NAM might be a promising alternative to using scopolamine alone in depression therapy, potentially allowing for a lower therapeutically effective dose. The common mechanism underlying the observed behavioral effects of the tested drugs may be associated with the modulation of the serotoninergic, glutamatergic, and dopaminergic systems.
临床研究证明,东莨菪碱是一种非选择性的毒蕈碱胆碱能受体拮抗剂,具有快速而持久的抗抑郁作用。然而,由于其显著的副作用,其作为精神药物的使用受到限制。一种有助于减少东莨菪碱副作用的治疗选择是与具有类似抗抑郁特性的其他物质以较低剂量共同施用。为了解决这个问题,我们通过强迫游泳试验(FST)和运动活动试验研究了东莨菪碱和mGlu2受体VU6001966的负变构调节剂对大鼠行为的影响。在自由活动大鼠中,用微透析法检测了给定化合物对大鼠额叶皮质(FCX)神经递质细胞外水平的影响。东莨菪碱和VU6001966在FST试验中均诱导剂量依赖性抗抑郁样作用,但不影响运动活动。此外,VU6001966提高细胞外多巴胺和血清素水平,同时降低谷氨酸,而不影响GABA水平。东莨菪碱单独或与VU6001966联合使用均可增加FCX中的多巴胺、血清素和谷氨酸水平,而不影响GABA水平。我们的研究结果表明,东莨菪碱与mGlu2 NAM联合施用可能是单独使用东莨菪碱治疗抑郁症的一种有希望的替代方法,可能允许较低的治疗有效剂量。所观察到的试验药物的行为效应的共同机制可能与血清素能、谷氨酸能和多巴胺能系统的调节有关。
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引用次数: 0
Astrocyte gap junction dysfunction activates JAK2-STAT3 pathway to mediate inflammation in depression 星形胶质细胞间隙连接功能障碍激活JAK2-STAT3通路介导抑郁症炎症。
IF 3.3 3区 心理学 Q1 BEHAVIORAL SCIENCES Pub Date : 2025-03-05 DOI: 10.1016/j.pbb.2025.173987
Xue-Ying Yang , Hui-Qin Wang , Meng-Zhang , Ai-Ping Chen , Xin-Mu Li , Zan Xing , Hong Jiang , Xu Yan , Shi-Feng Chu , Zhen-Zhen Wang , Nai-Hong Chen
Connexin 43 (Cx43) is highly expressed in astrocytes and forms gap junctions that maintain intercellular communication. Dysfunctional gap junctions in astrocytes exacerbate depressive symptoms, which has been implicated in the pathogenesis of depression. Inflammatory responses occur in the brains of most people with depression. However, it is unclear whether dysfunctional astrocyte gap junctions mediate the onset of the inflammatory response in the brains of depressed patients. Transporter protein (TSPO), the most common neuroinflammatory marker and a novel target of antidepressants identified in recent years, is mainly expressed by glial cells in the brain and is abnormally upregulated during inflammatory activation. We found that in a mouse model of chronic unpredictable stress (CUS), astrocyte gap junctions in the prefrontal cortex are impaired and the JAK2-STAT3 signaling pathway is activated, leading to an increase in the inflammatory marker TSPO. Based on this finding, we further verified using Cx43 transgenic mice that conditional knockdown of Cx43 in prefrontal cortex astrocytes also activated the JAK2-STAT3 inflammatory signaling pathway, with concomitant elevated levels of the inflammatory marker TSPO, and the mice developed depressive-like behavior. In contrast, impaired corticosterone (CORT)-induced gap junction function and increased TSPO were ameliorated by the JAK2-STAT3 inhibitor protosappanin A (PTA). Thus, targeting astrocyte Cx43 attenuates the inflammatory response in depression and improves depressive symptoms. This provides a new perspective on the pathogenesis of depression and a new therapeutic target for antidepressant research.
连接蛋白43 (Cx43)在星形胶质细胞中高表达,形成维持细胞间通讯的间隙连接。星形胶质细胞中功能失调的间隙连接加剧了抑郁症状,这与抑郁症的发病机制有关。大多数抑郁症患者的大脑都有炎症反应。然而,目前尚不清楚功能失调的星形胶质细胞间隙连接是否介导了抑郁症患者大脑炎症反应的发生。转运蛋白(Transporter protein, TSPO)是近年来发现的最常见的神经炎症标志物和抗抑郁药物的新靶点,主要由脑胶质细胞表达,在炎症激活过程中异常上调。我们发现,在小鼠慢性不可预测应激(CUS)模型中,前额叶皮层的星形胶质细胞间隙连接受损,JAK2-STAT3信号通路被激活,导致炎症标志物TSPO增加。基于这一发现,我们利用Cx43转基因小鼠进一步证实,前额皮质星形胶质细胞中Cx43的条件性敲低也激活了JAK2-STAT3炎症信号通路,同时炎症标志物TSPO水平升高,小鼠出现抑郁样行为。相比之下,皮质酮(CORT)诱导的间隙连接功能受损和TSPO升高可以通过JAK2-STAT3抑制剂原皂苷A (PTA)得到改善。因此,靶向星形胶质细胞Cx43可减轻抑郁症中的炎症反应并改善抑郁症状。这为研究抑郁症的发病机制提供了新的视角,也为抗抑郁药物的研究提供了新的治疗靶点。
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引用次数: 0
Standardization of decision-making skills but persistent impulsivity after chronic stimulant exposure in ADHD patients ADHD患者慢性兴奋剂暴露后决策技能的标准化和持续性冲动
IF 3.3 3区 心理学 Q1 BEHAVIORAL SCIENCES Pub Date : 2025-02-26 DOI: 10.1016/j.pbb.2025.173986
Francisco José Lobato-Camacho, Juan Pedro Vargas, Juan Carlos López
Attention deficit hyperactivity disorder (ADHD) is commonly associated with deficits in executive function. Even though attention, hyperactivity, and impulsivity are the more distinctive symptoms, impairment in other cognitive processes, for instance memory, could be due to the interferences from these symptoms. However, it remains unclear whether information processing errors made by individuals with ADHD arise primarily from impulsive responding or reflect a more fundamental difference in how they process information, potentially due to compensatory mechanisms developed throughout childhood. This study analyzes pattern separation (distinguishing similar stimuli), recognition memory, decision-making, and impulsivity in both ADHD-diagnosed and non-diagnosed youth population. We further examined possible treatment effects by dividing the ADHD group into three cohorts based on stimulant medication duration. We evaluate their response latency and responses utilizing the signal detection theory method. While ADHD participants exhibited poorer recognition memory compared to controls, this pattern did not show a statistically significant difference in pattern separation. Additionally, both processes improved with longer treatment duration within the ADHD group, leading to decreased error commission. Decision-making analyses revealed sex-specific response strategies within the ADHD group, but both groups showed similar adjustment to task difficulty. However, the ADHD group responses were notably faster, associated with a higher error rate. Additionally, response times varied depending on the stimulus type, suggesting potential differences in how the ADHD group processed information compared to the control group. These findings collectively point towards a possible difference in information management in ADHD, that is also characterized by faster, but less accurate, processing.
注意缺陷多动障碍(ADHD)通常与执行功能缺陷有关。尽管注意力、多动和冲动是更明显的症状,但其他认知过程的损害,例如记忆,可能是由于这些症状的干扰。然而,目前尚不清楚的是,ADHD患者的信息处理错误主要是由冲动反应引起的,还是反映了他们处理信息的更根本的差异,这可能是由于整个童年时期发展起来的补偿机制。本研究分析了adhd诊断和非诊断青少年人群的模式分离(区分相似刺激)、识别记忆、决策和冲动。我们进一步研究了可能的治疗效果,根据兴奋剂用药时间将ADHD组分为三组。我们利用信号检测理论方法评估了它们的响应延迟和响应。与对照组相比,ADHD参与者表现出较差的识别记忆,但这种模式在模式分离方面没有统计学上的显著差异。此外,在ADHD组中,这两个过程都随着治疗时间的延长而改善,导致错误发生率降低。决策分析揭示了ADHD组的性别特异性反应策略,但两组对任务难度的调整相似。然而,ADHD组的反应明显更快,错误率也更高。此外,反应时间因刺激类型而异,这表明ADHD组与对照组在处理信息的方式上存在潜在差异。这些发现共同指出了ADHD患者在信息管理方面可能存在的差异,ADHD患者的信息处理速度更快,但准确性较低。
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引用次数: 0
Switching from menthol to non-menthol cigarettes does not impact acute responses to intravenous nicotine 从薄荷香烟转向不含薄荷香烟不会影响静脉注射尼古丁的急性反应
IF 3.3 3区 心理学 Q1 BEHAVIORAL SCIENCES Pub Date : 2025-02-24 DOI: 10.1016/j.pbb.2025.173985
Noah R. Wolkowicz , Suprit Parida , Ralitza Gueorguieva , Mehmet Sofuoglu

Background

Limited research exists on how switching from menthol to non-menthol cigarettes affects the acute response to nicotine for individuals who smoke menthol cigarettes. Such research can inform public health strategies to reduce smoking prevalence.

Aims

This study investigated whether switching from menthol to non-menthol cigarettes for two weeks alters the acute responses to intravenous nicotine infusions delivered at different rates. We assessed changes in subjective drug effects, smoking urges, withdrawal severity, heart rate, and performance on the Continuous Performance Test (CPT) (primary outcomes); as well as nicotine biomarker blood levels (ng/ml) of nicotine, cotinine, and nicotine metabolite ratio (NMR; hydroxycotinine/cotinine), and cigarette consumption (secondary outcomes).

Methods

Sixteen menthol-preferring individuals who smoke cigarettes were randomized to a sequence of menthol or non-menthol cigarette smoking conditions for 2 weeks (Phase 1) and then switched to the other condition for another 2 weeks (Phase 2). During week 2 of each phase, an experimental session was held. During the experimental sessions, participants were given a total of 3 infusions, one saline and two nicotine infusions delivered at different rates (1 mg nicotine delivered over 2.5- and 5-min). Each infusion period lasted 10 min, with saline administered for the remainder of the time after the 2.5- and 5-min nicotine infusions. Following the first session, participants crossed over to the other smoking condition.

Results

Switching to non-menthol cigarettes led to a decrease in daily cigarette smoking (p < .05). However, this switch did not appear to affect the severity of tobacco withdrawal, urges to smoke, or the subjective and heart rate responses to IV nicotine administration (p > .05).

Conclusions

These findings suggest that switching from menthol to non-menthol cigarettes is feasible without significantly altering the individual's response to nicotine. Further, there may be a potential public health benefit through reduced cigarette consumption.
关于从薄荷香烟转向非薄荷香烟如何影响吸薄荷香烟的人对尼古丁的急性反应的研究有限。这种研究可以为公共卫生战略提供信息,以减少吸烟率。目的:本研究调查了在两周内从薄荷香烟切换到非薄荷香烟是否会改变静脉注射尼古丁的急性反应。我们评估了主观药物效应、吸烟冲动、戒断严重程度、心率和持续表现测试(CPT)表现的变化(主要结局);以及尼古丁、可替宁的血液生物标志物水平(ng/ml)和尼古丁代谢物比率(NMR;羟可替宁/可替宁)和吸烟(次要结局)。方法将16名嗜薄荷醇者随机分为两组(第一阶段),分别吸烟薄荷醇组和非薄荷醇组,两周后切换到另一组(第二阶段)。在每一阶段的第二周进行一次实验。在实验期间,参与者共接受3次输注,1次生理盐水输注和2次尼古丁输注,输注速度不同(1毫克尼古丁在2.5分钟和5分钟内输注)。每次输注持续10分钟,在2.5分钟和5分钟尼古丁输注后的剩余时间给予生理盐水。在第一阶段之后,参与者转入另一种吸烟状态。结果改用不含薄荷醇的香烟导致每日吸烟量减少(p <;. 05)。然而,这种转变似乎并没有影响戒烟的严重程度,吸烟的冲动,或对静脉注射尼古丁的主观和心率反应(p >;. 05)。这些发现表明,从薄荷香烟转向不含薄荷香烟是可行的,而不会显著改变个人对尼古丁的反应。此外,减少香烟消费可能对公众健康有潜在的好处。
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引用次数: 0
期刊
Pharmacology Biochemistry and Behavior
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