Pharmacology Biochemistry and Behavior最新文献_第4页

Caffeine intake during gestation and lactation causes long-term behavioral impairments in heterogenic mice offspring in a sex-dependent manner 妊娠期和哺乳期摄入咖啡因会导致异源小鼠后代的长期行为障碍。

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-02-01 DOI: 10.1016/j.pbb.2024.173949

Bruna da Silva Oliveira , Thaís de Mérici Domingues Paula , Lucas Carvalho Cardoso , João Vitor Lopes Ferreira , Caroline Amaral Machado , Heliana de Barros Fernandes , Brener Cunha Carvalho , Ingrid dos Santos Freitas , Lorena Taveira Nogueira , Antônio Lúcio Teixeira , Eliana Cristina de Brito Toscano , Aline Silva de Miranda , Fernanda Radicchi Campos Lobato de Almeida

Growing evidence has indicated a potential association between maternal consumption of caffeine and impaired cognition and behavior in rodent offspring. However, potential sex differences, as well as caffeine-related effects in subsequent generations are still poorly investigated. We aimed to investigate the impact of pre-and/or neonatal exposition to caffeine on the neurodevelopment of male and female mice offspring. Adult female Swiss mice were randomly divided into four experimental groups, which received, via gavage, water or caffeine (120 mg/day). Control/control (CC) received water during pregnancy and lactation; treated/control (TC): received caffeine during pregnancy and water during lactation; control/treated (CT): received water during pregnancy and caffeine during lactation; treated/treated (TT): received caffeine during pregnancy and lactation. Dams were euthanized at gestational day 17.5 and fetal brains were collected. Adult mice of F1 and F2 generations were submitted to behavioral analysis and their pre-frontal cortex and hippocampi were dissected to measure the levels of BDNF and CX3CL1. Caffeine induced reduction of CX3CL1 levels in female fetuses compared with controls. Maternal intake of caffeine was associated with anxiety- and compulsive-like behavior in both F1 and F2 female mice offspring. Interestingly, only F2 female mice exhibited caffeine-induced impairment of work memory. Hippocampal levels of CX3CL1 and BDNF were decreased in female F1TT and F2TT groups; while among males exposed to caffeine, only F1 offspring had reduced hippocampal CX3CL1 levels. Our results suggest that both pre- and neonatal exposition to caffeine lead to long-term behavioral and neurochemical impairments in a sex-dependent manner, adversely affecting the subsequent female generation.

越来越多的证据表明，母体摄入咖啡因与啮齿动物后代的认知和行为受损之间存在潜在联系。然而，潜在的性别差异，以及咖啡因对后代的影响，研究仍然很少。我们的目的是调查前和/或新生儿接触咖啡因对雄性和雌性小鼠后代神经发育的影响。将成年瑞士雌性小鼠随机分为4个实验组，分别给予水或咖啡因（120 mg/天）灌胃。对照组/对照组（CC）在妊娠期和哺乳期饮水；实验组/对照组（TC）：在怀孕期间摄入咖啡因，在哺乳期摄入水；对照组/实验组（CT）：在怀孕期间喝水，在哺乳期摄入咖啡因；治疗/治疗（TT）：在怀孕和哺乳期接受咖啡因。在妊娠17.5天对母鼠实施安乐死，并收集胎儿脑。对F1和F2代成年小鼠进行行为分析，并解剖其前额叶皮层和海马，测量BDNF和CX3CL1的水平。与对照组相比，咖啡因诱导雌性胎儿CX3CL1水平降低。在F1和F2雌性小鼠的后代中，母体摄入咖啡因与焦虑和强迫行为有关。有趣的是，只有F2只雌性小鼠表现出咖啡因引起的工作记忆损伤。女性F1TT和F2TT组海马CX3CL1和BDNF水平降低；而在接触咖啡因的雄性中，只有F1后代的海马CX3CL1水平降低。我们的研究结果表明，产前和新生儿接触咖啡因都会导致性别依赖的长期行为和神经化学损伤，对后代的雌性后代产生不利影响。

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引用次数: 0

Juvenile chronic social defeat stress reduces prosocial behavior in adult male mice 幼鼠慢性社会失败压力会降低成年雄鼠的亲社会行为。

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-02-01 DOI: 10.1016/j.pbb.2024.173941

Zihan Zhao , Mingxu Zhang , Qiqi Tang , Minghao Lu , Xiangyu An , Yajie Cui , Mingyang Zhao , Ningyuan Qian , Juan Shao , Haishui Shi , Xiaojuan Qie , Li Song

Exposure to stress in early life can have a significant impact on individuals. However, the effects of early-life stress (ELS) on prosocial behavior remain unclear, as do the underlying mechanisms. In this study, ICR juvenile mice were subjected to juvenile chronic social defeat stress (jCSDS) between postnatal days 32 and 41, during which body weight changes were continuously monitored. The behaviors of adult mice were evaluated using the open field test (OFT), the social interaction test (SIT), and the prosocial choice task (PCT). ELISA was used to quantify serum levels of oxytocin, serotonin, and dopamine. The density of dendritic spines in the basolateral amygdala was evaluated by Golgi staining. Behavioral test results showed that jCSDS induced anxiety-like behavior and decreased prosocial selection tendency in mice. Additionally, exposure to jCSDS increased the serum levels of oxytocin, decreased those of serotonin, and increased the density of dendritic spines in the basolateral amygdala. Correlation analysis indicated that prosocial behavior was negatively correlated with serum oxytocin levels and dendritic spine density in the basolateral amygdala. These results suggested that jCSDS reduced prosocial behavior, possibly due to changes in serum oxytocin contents and adaptive changes in amygdaloid neurons.

早期生活中的压力会对个人产生重大影响。然而，早期生活压力（ELS）对亲社会行为的影响及其潜在机制尚不清楚。在本研究中，ICR幼年小鼠在出生后第32天至第41天遭受幼年慢性社会失败应激（jCSDS），在此期间连续监测体重变化。采用开放场测验（open field test， OFT）、社会互动测验（social interaction test， SIT）和亲社会选择任务（pro - social choice task， PCT）评估成年小鼠的行为。ELISA测定血清中催产素、血清素和多巴胺的水平。高尔基染色测定杏仁核基底外侧树突棘密度。行为学测试结果显示，jCSDS诱导小鼠焦虑样行为，降低亲社会选择倾向。此外，暴露于jCSDS增加血清催产素水平，降低血清血清素水平，并增加杏仁核基底外侧树突棘的密度。相关分析表明，亲社会行为与血清催产素水平和杏仁核基底外侧树突棘密度呈负相关。这些结果表明，jCSDS降低了亲社会行为，可能是由于血清催产素含量的改变和杏仁核神经元的适应性改变。

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引用次数: 0

Elucidating the alcohol-sleep-hangover relationship in college students using a daily diary approach 利用每日日记法阐明大学生的酒精-睡眠-宿醉关系。

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-02-01 DOI: 10.1016/j.pbb.2024.173910

Neel Muzumdar , Kristina M. Jackson , Jennifer F. Buckman , Andrea M. Spaeth , Alexander W. Sokolovsky , Anthony P. Pawlak , Helene R. White

This daily diary study expands knowledge of the pharmacological alcohol-sleep relationship using a multilevel modeling approach. The interplay between alcohol and sleep on hangover susceptibility is also explored. College students (n = 337; 52 % female) provided 2976 days of self-reported alcohol use. We regressed sleep duration onto accumulated sleep debt, prior night sleep duration, and estimated blood alcohol concentration (eBAC) at bedtime; linear mixed models disaggregated day and person-level effects. Binomial models, assessing days after drinking when eBAC = 0 % versus when eBAC>0 % at waketime, regressed hangover susceptibility onto the same predictors plus sleep duration. More accumulated sleep debt predicted slightly longer same-night sleep. Greater than average bedtime intoxication predicted longer than average same-night sleep when drinking ceased early, but later drinking attenuated the relationship. People who typically stopped drinking later in the night reported typically shorter sleep durations on drinking nights. When waketime eBAC = 0 %, higher eBAC at bedtime and drinking later on a given night predicted greater next-day hangover susceptibility. Typical bedtime eBAC and typically later drinking predicted typically greater hangover susceptibility. When waketime eBAC>0 %, longer sleep duration predicted more likely hangovers. Bedtime eBAC and sleep debt interacted, such that more sleep debt attenuated the positive association between intoxication and next-day hangover susceptibility. Late-night drinking appeared to reduce sleep duration and increase hangover susceptibility. Accumulated sleep debt complicated the alcohol-sleep-hangover relationship. External factors influencing sleep behaviors were not assessed, but the results highlight the need to deconstruct sleep into acute and chronic processes. Future studies should better subdivide physiological processes related to hangovers.

这项每日日记研究采用多层次建模方法，扩展了对药理酒精与睡眠关系的认识。研究还探讨了酒精和睡眠对宿醉易感性的相互作用。大学生（n = 337；52 % 为女性）提供了 2976 天的自我报告饮酒情况。我们将睡眠时间与累积睡眠负债、前一晚睡眠时间和睡前估计血液酒精浓度（eBAC）进行了回归；线性混合模型对日效应和人效应进行了分解。二项式模型评估了饮酒后 eBAC = 0 % 与清醒时 eBAC>0 % 的天数，将宿醉易感性回归到相同的预测因素和睡眠时间上。累积的睡眠债务越多，则当晚睡眠时间越长。如果较早停止饮酒，睡前醉酒程度高于平均水平，则当晚睡眠时间也会比平均水平长，但较晚停止饮酒则会减弱这种关系。通常在晚些时候停止饮酒的人在饮酒当晚的睡眠时间通常较短。当清醒时 eBAC = 0 % 时，睡前 eBAC 较高和某晚较晚饮酒预示着第二天更容易宿醉。典型的睡前 eBAC 和典型的较晚饮酒预测了较高的宿醉易感性。当清醒时 eBAC>0 % 时，睡眠时间越长，宿醉的可能性越大。睡前 eBAC 和睡眠负债相互影响，因此睡眠负债越多，醉酒和次日宿醉易感性之间的正相关性就越小。深夜饮酒似乎缩短了睡眠时间，增加了宿醉的可能性。累积的睡眠债务使酒精-睡眠-宿醉之间的关系变得复杂。没有对影响睡眠行为的外部因素进行评估，但研究结果强调了将睡眠分解为急性和慢性过程的必要性。未来的研究应更好地细分与宿醉相关的生理过程。

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引用次数: 0

Microbiome depletion by broad-spectrum antibiotics does not influence demyelination and remyelination in cuprizone-treated mice 广谱抗生素对铜酮处理小鼠的脱髓鞘和再脱髓鞘没有影响。

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-02-01 DOI: 10.1016/j.pbb.2024.173946

Rumi Murayama , Guilin Liu , Ming-ming Zhao , Dan Xu , Ting-ting Zhu , Yi Cai , Yong Yue , Hiroyuki Nakamura , Kenji Hashimoto

Demyelination in the central nervous system (CNS) is a feature of various psychiatric and neurological disorders. Emerging evidence suggests that the gut-brain axis may play a crucial role in CNS demyelination. The cuprizone (CPZ) model, which involves the administration of CPZ-containing food pellets, is commonly used to study the effects of different compounds on CNS demyelination and subsequent remyelination. This study aimed to evaluate the impact of microbiome depletion, induced by an antibiotic cocktail (ABX), on demyelination in CPZ-treated mice and the subsequent remyelination following CPZ withdrawal. Our findings indicate that a chronic 4-week oral ABX regimen, administered both during and after a 6-week CPZ exposure, does not affect demyelination or remyelination in the brains of CPZ-treated mice. Specifically, ABX treatment for 2 weeks before and 2 weeks after CPZ exposure, in the final 4 weeks before sacrifice, and for 4 weeks post-CPZ withdrawal, did not significantly alter these processes compared to control mice receiving water instead of ABX. These results indicate that despite effective microbiome depletion, a 4-week oral ABX regimen does not influence demyelination or remyelination in the CPZ model. Thus, it is unlikely that gut microbiota depletion by ABX plays a significant role in these processes. However, further research is needed to fully understand the role of the host microbiome on CPZ-induced demyelination.

中枢神经系统脱髓鞘是各种精神和神经系统疾病的特征。新出现的证据表明，肠脑轴可能在中枢神经系统脱髓鞘中起关键作用。铜酮（CPZ）模型通常用于研究不同化合物对中枢神经系统脱髓鞘和随后的再髓鞘形成的影响，该模型涉及给药含CPZ的食物颗粒。本研究旨在评估抗生素鸡尾酒（ABX）诱导的微生物群枯竭对CPZ治疗小鼠脱髓鞘的影响，以及CPZ停药后的再髓鞘形成。我们的研究结果表明，在CPZ暴露6周期间和之后给予慢性4周口服ABX方案，不会影响CPZ治疗小鼠大脑中的脱髓鞘或再髓鞘形成。具体而言，与接受水而不是ABX的对照小鼠相比，在CPZ暴露前2 周和暴露后2 周、牺牲前最后4 周和CPZ退出后4 周，ABX治疗并没有显著改变这些过程。这些结果表明，尽管有效的微生物组消耗，4周口服ABX方案不会影响CPZ模型中的脱髓鞘或再髓鞘形成。因此，ABX引起的肠道菌群消耗不太可能在这些过程中起重要作用。然而，要充分了解宿主微生物群在cpz诱导的脱髓鞘中的作用，还需要进一步研究。

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引用次数: 0

Amplification of the therapeutic potential of AMPA receptor potentiators from the nootropic era to today

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-01-31 DOI: 10.1016/j.pbb.2025.173967

Daniel P. Radin , Arnold Lippa , Sabhya Rana , David D. Fuller , Jodi L. Smith , Rok Cerne , Jeffrey M. Witkin

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic receptors (AMPA receptors or AMPARs) are involved in fast excitatory neurotransmission and as such control multiple important physiological processes. AMPARs also are involved in the dynamics of synaptic plasticity in the nervous system where they impact neuroplastic responses such as long-term facilitation and long-term potentiation that regulate biological functions ranging from breathing to cognition. AMPARs also regulate neurotrophic factors that are strategically involved in neural plastic changes in the nervous system. As with other major ionotropic receptors, modulation of AMPARs can have prominent effects on biological systems that can include marked tolerability issues. AMPAR potentiators (AMPAkines) are positive allosteric modulators of AMPARs which have therapeutic potential. Medicinal chemistry combined with new pharmacological findings have defined AMPAkines with favorable oral bioavailability and pharmacological safety parameters that enable clinical advancement of their therapeutic utility. AMPAkines are being investigated in patients with diverse neurological and psychiatric disorders including spinal cord injury (breathing and bladder function), cognition, attention-deficit-hyperactivity disorder, and major depressive disorder. The present discussion of this class of compounds focuses on their general value as therapeutics through their impact on synaptic plasticity.

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引用次数: 0

Desvenlafaxine with mindfulness-based cognitive therapy reduces Hamilton anxiety scores compared to escitalopram with mindfulness-based cognitive therapy in treatment-resistant generalized anxiety disorder 在治疗难治性广泛性焦虑障碍中，与艾司西酞普兰联合正念认知疗法相比，地文拉法辛联合正念认知疗法可降低汉密尔顿焦虑评分。

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-01-19 DOI: 10.1016/j.pbb.2025.173959

Karthik Sankar , Sandhiya Ramesh , Natarajan Shanmugasundaram , Deepika Anbalagan , Varadharajan Sivaraman , Venkatesan Singaram , Srikanth Jeyabalan

Background

This study aims to assess the effectiveness of low-dose Escitalopram (10 mg) or low-dose Desvenlafaxine (25 mg) combined with mindfulness-based cognitive therapy (MBCT) in addressing challenges in treating generalized anxiety disorder (GAD), particularly in patients resistant to conventional therapies.

Methods

A prospective cohort study was conducted with individuals diagnosed with treatment-resistant GAD. group A included patients unresponsive to citalopram, imipramine, paroxetine, and sertraline, who were then treated with low-dose Escitalopram (10 mg) combined with MBCT. group B comprised those unresponsive to venlafaxine and duloxetine, who were treated with Desvenlafaxine (25 mg) alongside MBCT. Participants were monitored over 24 weeks for changes in Hamilton Anxiety Rating Scale (HAM-A) and Mindful Attention Awareness Scale (MAAS) scores, with medication adherence measured using the Medication Adherence Rating Scale (MARS). The primary outcomes focused on the improvement in anxiety symptoms and overall mental well-being.

Results

Comparative analysis between the groups showed significant improvement in HAM-A and MAAS scores at week 16 in group B compared to group A (P < 0.01). Within-group analysis also demonstrated a significant reduction in scores at week 12 in group B compared to group A at week 16 (P < 0.01). No significant difference was observed in medication adherence between the two groups (P = 0.122).

Conclusion

Patients treated with low-dose Desvenlafaxine combined with MBCT exhibited greater improvements in managing treatment-resistant GAD compared to those treated with low-dose Escitalopram. This approach highlights the potential for more inclusive and effective mental health strategies, contributing to enhanced quality of life and well-being.

背景：本研究旨在评估低剂量艾司西酞普兰（10 mg）或低剂量地文拉法辛（25 mg）联合正念认知疗法（MBCT）治疗广泛性焦虑障碍（GAD）的有效性，特别是对常规疗法有抗性的患者。方法：对诊断为难治性广泛性焦虑症的个体进行前瞻性队列研究。A组患者对西酞普兰、丙咪嗪、帕罗西汀、舍曲林无反应，给予低剂量艾司西酞普兰（10 mg）联合MBCT治疗。B组包括对文拉法辛和度洛西汀无反应的患者，他们在MBCT的同时接受地文拉法辛（25 mg）治疗。参与者在24 周内监测汉密尔顿焦虑评定量表（HAM-A）和正念注意意识量表（MAAS）得分的变化，并使用药物依从性评定量表（MARS）测量药物依从性。主要结果集中在焦虑症状和整体心理健康的改善上。结果：组间比较分析显示，与A组相比，B组在第16周的HAM-A和MAAS评分有显著改善（P ）。结论：低剂量地文拉法辛联合MBCT治疗的患者在治疗难治性GAD方面比低剂量艾司西酞普兰治疗的患者有更大的改善。这一方针强调了制定更具包容性和更有效的心理健康战略的潜力，有助于提高生活质量和福祉。

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引用次数: 0

NMDA-induced lesions of the nucleus accumbens core increase the innately rewarding saccharin solution intake and methamphetamine-induced conditioned place preference but not conditioned taste aversion in rats nmda诱导的伏隔核损伤增加了大鼠天生的奖励性糖精溶液摄入和甲基苯丙胺诱导的条件位置偏好，但不增加条件味觉厌恶。

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-01-13 DOI: 10.1016/j.pbb.2025.173957

Cai-N Cheng , Anna Kozłowska , Wei-Lun Li , Chi-Wen Wu , Ying-Chou Wang , Andrew Chih Wei Huang

The role of the nucleus accumbens (NAc) core in determining the valence of innately rewarding saccharin solution intake, methamphetamine (MAMPH)-induced conditioned taste aversion (CTA), and conditioned place preference (CPP) reward remains unclear. The present study utilized the “pre- and post-association” experimental paradigm (2010) to test whether the rewarding and aversive properties of MAMPH can be modulated by an N-methyl-D-aspartic acid (NMDA) lesion in the NAc core. Moreover, it tested how an NAc core NMDA lesion affected the innate reward of saccharin solution intake. The results demonstrate that MAMPH could simultaneously induce an aversive CTA and a rewarding CPP effect, supporting the paradoxical effect hypothesis of abused drugs, in particular amphetamine. Meanwhile, the NMDA-lesioned NAc core increased the reward effect of CPP but did not alter the aversive CTA effect. The NAc core NMDA lesion also enhanced the innate reward of saccharin solution intake. The NAc core therefore seemingly plays an inhibitory role in the innate reward of saccharin solution intake and in the CPP effect. The paradoxical effect hypothesis of abused drugs provides some explanations for the present data in the case of MAMPH administrations. The NAc core may play an essential role in modulating the rewarding but not the aversive properties of MAMPH. The present findings could contribute to the understanding and eventual advancement of clinical interventions for drug addiction and the development of novel pharmacological treatments.

伏隔核（NAc）核心在决定先天奖励糖精溶液摄入、甲基苯丙胺（MAMPH）诱导的条件味觉厌恶（CTA）和条件位置偏好（CPP）奖励的效价中的作用尚不清楚。本研究利用“前后关联”实验范式（2010）来测试NMDA在NAc核心的损伤是否可以调节MAMPH的奖励和厌恶特性。此外，它还测试了NAc核心NMDA损伤如何影响糖精溶液摄入的先天奖励。结果表明，MAMPH可以同时诱导不良的CTA和有益的CPP效应，支持滥用药物的矛盾效应假说，特别是安非他明。同时，nmda损伤的NAc核增加了CPP的奖励效应，但没有改变CTA的厌恶效应。NAc核心NMDA损伤也增强了糖精溶液摄入的先天奖励。因此，NAc核心似乎在糖精溶液摄入的先天奖励和CPP效应中起抑制作用。滥用药物的矛盾效应假说为目前的数据提供了一些解释。NAc核心可能在调节MAMPH的奖赏性而非厌恶性方面发挥重要作用。本研究结果有助于理解和最终推进药物成瘾的临床干预措施和开发新的药物治疗方法。

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引用次数: 0

Differential reductions in alcohol consumption and cue-induced alcohol-seeking behavior following mGlu5 receptor inhibition in the prelimbic vs. infralimbic subregions of the rat prefrontal cortex 在大鼠前额叶皮层的边缘前区和边缘下亚区，mGlu5受体抑制后，酒精消耗和线索诱导的酒精寻求行为的差异减少。

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-01-11 DOI: 10.1016/j.pbb.2025.173958

Jonna M. Leyrer-Jackson , Peter R. Kufahl , M. Foster Olive

Glutamatergic signaling is one of the primary targets of actions of alcohol in the brain, and dysregulated excitatory transmission in the prefrontal cortex (PFC) may contribute problematic drinking and relapse. A prominent component of glutamate signaling is the type 5 metabotropic glutamate (mGlu5) receptor. However, little is known about the role of this receptor type in subregions of the PFC that regulate either alcohol intake or alcohol-seeking behavior. Here we examined the effects of microinfusions of the selective mGlu5 inhibitor 3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine (MTEP) into either the prelimbic (PL) or infralimbic (IL) regions of the PFC on alcohol intake or cue-evoked reinstatement of alcohol-seeking behavior. Adult male Wistar rats were trained to self-administer 10 % alcohol in the presence of compound discriminative stimuli (SD) signaling alcohol availability (S+) or non-availability (S-). In one group of animals, effects of locally administered MTEP (0, 0.5 or 1 μg/μl) into either the PL or IL on active alcohol intake were examined. MTEP was without effect on alcohol self-administration when infused into the PL, but decreased alcohol intake at both doses tested when infused into the IL. In separate groups of animals, we examined effects of locally administered MTEP (0, 0.5 or 1 μg/μl) into either the PL or IL on reinstatement of alcohol seeking elicited by alcohol predictive stimuli (S+). When infused into the PL, MTEP attenuated cue-induced reinstatement only at the higher dose tested (1 μg/μl), but when infused into the IL, MTEP reduced cue-induced reinstatement at both doses tested (0.5 μg/μl and 1 μg/μl). Together, these results suggest a largely preferential role for mGlu5 signaling in the IL vs. PL in regulating both alcohol self-administration behavior and cue-elicited alcohol seeking. Neuromodulatory approaches aimed at reducing mGlu5 signaling in the IL may therefore be of potential therapeutic value in problematic alcohol use.

谷氨酸能信号是酒精在大脑中作用的主要目标之一，前额叶皮层（PFC）兴奋性传递失调可能导致饮酒问题和复发。谷氨酸信号传导的一个重要组成部分是5型代谢型谷氨酸（mGlu5）受体。然而，这种受体类型在调节酒精摄入或寻求酒精行为的PFC亚区中所起的作用知之甚少。在这里，我们研究了将选择性mGlu5抑制剂3-（（2-甲基-1,3-噻唑-4-基）乙基）吡啶（MTEP）微量注入PFC的边缘前区（PL）或边缘下区（IL）对酒精摄入或线索诱发的酒精寻求行为恢复的影响。成年雄性Wistar大鼠接受训练，在有酒精可用性（S+）或不可用性（S-）信号的复合鉴别刺激（SD）存在的情况下自我服用10 %酒精。在一组动物中，研究了局部给药MTEP（0、0.5或1 μl）到PL或IL中对活性酒精摄入量的影响。当将MTEP输注到PL中时，对酒精自我给药没有影响，但当输注到IL中时，两种剂量的MTEP都减少了酒精摄入量。在不同的动物组中，我们研究了局部给药MTEP（0、0.5或1 μl）在PL或IL中对酒精预测刺激（S+）引起的酒精寻求恢复的影响。MTEP只在大剂量（1 μl）下降低了大剂量（0.5 μl和1 μl）下的提示恢复，而在大剂量（0.5 μl和1 μl）下均降低了提示恢复。总之，这些结果表明mGlu5信号在IL和PL中在调节酒精自我给药行为和线索诱导的酒精寻求方面具有很大的优先作用。因此，旨在减少IL中mGlu5信号的神经调节方法可能对问题性酒精使用具有潜在的治疗价值。

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引用次数: 0

Simultaneous activation of different subtypes of dopamine receptors may lead to activation of homeostatic sleep regulatory mechanisms 同时激活不同亚型多巴胺受体可能导致激活稳态睡眠调节机制。

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-01-10 DOI: 10.1016/j.pbb.2025.173954

Dóra Keserű , Tünde Hajnik , Máté Pethő , László Détári , Maarten Van Den Bossche , Attila Tóth

Dopaminergic system gains importance in homeostatic sleep regulation, but the role of different dopamine receptors is not well-defined. 72 h rat electrocorticogram and sleep recordings were made after single application of dopaminergic drugs in clinical use or at least underwent clinical trials. The non-selective agonist apomorphine evoked short pharmacological sleep deprivation with intense wakefulness followed by pronounced sleep rebound. D2 agonist bromocriptine induced moderate and extended increase in wakefulness without a homeostatic sleep replacement but downregulated slow wave sleep need for 72 h. Selective D1 agonist SKF-38393 failed to induce enhanced waking sufficient for sleep replacement. High-dose D2 antagonism by sulpiride temporarily enhanced wakefulness. All drugs evoked extended (72 h) sleep changes after single application. Opposite sleep changes could be seen after the application of different doses in case of both bromocriptine and sulpiride.

Theta, beta and gamma power reflected intensity differences in drug-induced wakefulness stages. Apomorphine- and high sulpiride dose-induced waking showed elevated power in all three frequency bands. Bromocriptine-induced wakefulness dominated by beta activity. Enhancement of more, than one type of electrocorticogram activities during wakefulness was a prerequisite for the activation of sleep homeostasis.

According to present data, D1- or D2-like receptor agonism are not separately involved in the homeostatic regulation of slow wave sleep. Simultaneous and non-selective agonism on DA receptors is the most effective way to elicit intense W, which is followed by slow wave sleep rebound. REM sleep rebound could be evoked by D2 agonism. Rebound indicates the activation of homeostatic sleep regulation, but with unknown exact mechanisms.

多巴胺能系统在稳态睡眠调节中占有重要地位，但不同多巴胺受体的作用尚不明确。72 h大鼠在临床应用单次多巴胺能药物或至少进行临床试验后进行皮质电图和睡眠记录。非选择性激动剂阿波啡引起短暂的药理学睡眠剥夺，伴有强烈的清醒，随后出现明显的睡眠反弹。D2激动剂溴隐亭诱导清醒度中度和延长增加，无稳态睡眠替代，但慢波睡眠需求下调72 h。选择性D1激动剂SKF-38393未能诱导足以替代睡眠的增强清醒。舒必利大剂量D2拮抗剂暂时增强清醒。单次用药后，所有药物均诱发延长（72 h）睡眠变化。溴隐亭和舒必利应用不同剂量后出现相反的睡眠变化。θ、β和γ能量反映了药物诱导觉醒阶段的强度差异。阿波吗啡和高剂量舒必利诱导的清醒在所有三个频带中均显示功率升高。溴隐亭诱导的觉醒以β活动为主。在清醒时，多种类型的皮质电图活动的增强是激活睡眠稳态的先决条件。根据目前的资料，D1或d2样受体激动作用并不单独参与慢波睡眠的稳态调节。同时和非选择性的对DA受体的激动作用是诱发高强度W的最有效方式，而高强度W随后是慢波睡眠反弹。D2激动作用可诱发快速眼动睡眠反弹。反弹表明激活了体内平衡睡眠调节，但其确切机制尚不清楚。

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引用次数: 0

Photobiomodulation using an 830-nm laser alleviates hippocampal reactive gliosis and cognitive dysfunction in a mouse model of adolescent chronic alcohol exposure 在青少年慢性酒精暴露小鼠模型中，使用830 nm激光进行光生物调节可减轻海马反应性胶质细胞增生和认知功能障碍。

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2025-01-09 DOI: 10.1016/j.pbb.2025.173956

Namgue Hong , Sung-Ryeong Yoon , Jin-Chul Ahn

Chronic alcoholism is known to have detrimental effects on the brain, including cognitive impairment, neurotransmitter imbalances, and brain atrophy. The hippocampus, crucial for spatial memory and cognitive functions, is particularly susceptible to alcohol-induced changes. Photobiomodulation (PBM), a non-invasive therapeutic method that utilizes red or near-infrared light, has shown promising applications in the central and peripheral nervous systems. Near-infrared (NIR) light, in particular, has been shown to prevent apoptosis, and neuroinflammation, as well as to improve cognitive functions. In this study, we aimed to investigate whether 830-nm laser irradiation could mitigate cognitive deficits in a chronic alcohol mouse model. Chronic alcoholism was induced in C57BL/6 mice through continuous ethanol gavage for 4 weeks at a dosage of 5 g/kg/day. Gavaging was performed 3 times per week for 4 weeks. Mice were transcranial irradiated by 830-nm laser, following making a chronic alcohol mouse model. Laser irradiation (50 mW/cm²) was performed 5 times per week for 3 weeks. To verify memory and cognitive defeats of a chronic alcohol mouse model, we performed animal behavior tasks such as Morris water maze, Y maze, and novel objective recognition. Our results confirmed the cognitive impairment in the chronic alcohol mouse model compared to the control group in conducted tasks. However, cognitive and spatial memory significantly improved following 830-nm laser irradiation. Additionally, we confirmed whether the behavior tasks result from histological changes. We performed immunofluorescence staining in the hippocampus region (CA3, CA1 and hilus) using astrocyte (GFAP) and microglia (Iba1) markers. As a result, reactive astrocyte was significantly increased in the chronic alcohol mouse model compared to control mice, whereas the number of GFAP-positive cells was significantly reduced by 830-nm laser irradiation. These findings indicate that chronic alcohol exposure induces spatial memory and cognitive impairment, which can be effectively rescued through near-infrared laser irradiation.

众所周知，慢性酒精中毒对大脑有有害影响，包括认知障碍、神经递质失衡和脑萎缩。对空间记忆和认知功能至关重要的海马体特别容易受到酒精引起的变化的影响。光生物调节（PBM）是一种利用红光或近红外光的非侵入性治疗方法，在中枢和周围神经系统中有很好的应用前景。特别是近红外（NIR）光，已被证明可以防止细胞凋亡和神经炎症，以及改善认知功能。在这项研究中，我们旨在研究830纳米激光照射是否可以减轻慢性酒精小鼠模型的认知缺陷。以5 g/kg/d的剂量连续灌胃4 周，诱导C57BL/6小鼠慢性酒精中毒。每周灌胃3次，共4 周。用830 nm激光经颅照射小鼠，建立慢性酒精小鼠模型。激光照射（50 mW/cm2），每周5次，共3 周。为了验证慢性酒精小鼠模型的记忆和认知失败，我们进行了动物行为任务，如莫里斯水迷宫、Y迷宫和新的客观识别。我们的研究结果证实，与对照组相比，慢性酒精小鼠模型在执行任务时存在认知障碍。然而，认知和空间记忆在830nm激光照射后显著改善。此外，我们还证实了行为任务是否由组织学改变引起。我们使用星形胶质细胞（GFAP）和小胶质细胞（Iba1）标记物对海马区（CA3、CA1和海门）进行免疫荧光染色。结果，与对照组小鼠相比，慢性酒精小鼠模型中的活性星形胶质细胞显著增加，而830 nm激光照射可显著减少gmap阳性细胞的数量。上述结果表明，慢性酒精暴露可引起空间记忆和认知功能障碍，近红外激光照射可有效恢复这些障碍。

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引用次数: 0