Pharmacology Biochemistry and Behavior最新文献_第2页

Dual activation of 5-HT1A and μ-opioid receptors mediates dezocine's antidepressant effects in mice with comorbid pain and depression 5-HT1A和μ-阿片受体的双重激活介导地佐辛对疼痛和抑郁共病小鼠的抗抑郁作用。

IF 2.5 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2026-02-01 Epub Date: 2025-12-07 DOI: 10.1016/j.pbb.2025.174136

Qian-Qian Wei , Kun-Hong Zhong , Xiao-Ke Zhang , Liangxue Zhou , Qing Zhu , Junxu Li

Background

Pain-depression morbidity affects millions, but there are no effective treatments available. Dezocine is a clinically used opioid analgesic with complicated pharmacological mechanisms. Given this unique pharmacological profile and the crucial involvement of noradrenergic/serotonergic systems in the pathophysiology of depression, dezocine might be able to relieve pain-depression comorbidity. This possibility has not been tested and is the focus of this study. However, this potential has not yet been empirically validated, and investigating it constitutes the primary aim of this study.

Methods

Animal models of depression (Lipopolysaccharides [LPS] and chronic unpredictable mild stress models [CUMS]) were established, and two neuropathic pain models (chronic constriction injury [CCI] and spared nerve injury [SNI]) were used to establish chronic pain-induced depressive-like behaviors and the antidepressive-like effects of dezocine were then examined. Tail suspension test (TST) and force swimming test (FST) were used as behavioral readouts of antidepressant effects. For receptor mechanisms studies, 5-HT_1A receptor antagonist WAY-100635, nonselective opioid receptor antagonist naltrexone [NTX]), and three selective opioid receptor antagonists (μ: CTAP; δ: naltrindole [NAL]; k: nor-binaltorphimine [nor-BNI]) were used as pretreatment to antagonize the effects of dezocine.

Results

Dezocine (5 and 10 mg/kg, i.p.) significantly reduced immobility time, suggesting its robust antidepressive-like effects in stand-alone depression models and in neuropathic pain-induced depression models. WAY-100635, NTX, and CTAP but not NAL or nBNI blocked the antidepressive-like effects of dezocine, suggesting the involvement of 5-HT_1A and μ-opioid receptors in mediating the antidepressive-like effects of dezocine.

Conclusion

This study demonstrates that dezocine alleviates pain-depression comorbidity by activating both 5-HT_1A and μ-opioid receptor.

背景：数百万人患有疼痛抑郁症，但目前尚无有效的治疗方法。地佐辛是临床上常用的阿片类镇痛药，其药理机制复杂。考虑到这种独特的药理学特征和去甲肾上腺素能/血清素能系统在抑郁症病理生理中的重要作用，地佐辛可能能够缓解疼痛-抑郁共病。这种可能性尚未得到验证，这是本研究的重点。然而，这种潜力尚未得到实证验证，调查它构成了本研究的主要目的。方法：建立抑郁动物模型（脂多糖[LPS]和慢性不可预测轻度应激模型[CUMS]），并采用两种神经性疼痛模型（慢性收缩损伤[CCI]和余留神经损伤[SNI]）建立慢性疼痛诱导的抑郁样行为，并检测地佐辛的抗抑郁样作用。用悬尾试验（TST）和用力游泳试验（FST）作为抗抑郁药效果的行为读数。受体机制研究采用5-HT1A受体拮抗剂WAY-100635、非选择性阿片受体拮抗剂纳曲酮（NTX）和3种选择性阿片受体拮抗剂（μ: CTAP、δ：纳曲多[NAL]、k：非-binaltorphimine [no - bni]）作为预处理，拮抗地佐辛的作用。结果：地佐辛（5和10 mg/kg， i.p）显著减少静止时间，提示其在独立抑郁模型和神经性疼痛性抑郁模型中具有强大的抗抑郁样作用。WAY-100635、NTX和CTAP阻断了地佐嗪的抗抑郁样作用，NAL和nBNI未阻断，提示5-HT1A和μ-阿片受体参与了地佐嗪的抗抑郁样作用。结论：地佐辛通过激活5-HT1A和μ-阿片受体减轻疼痛-抑郁共病。

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引用次数: 0

Peripubertal PTSD-like stress in rats induces transient behavioral but lasting metabolic and inflammatory alterations: Limited fluoxetine efficacy 大鼠青春期ptsd样应激诱导短暂的行为改变但持久的代谢和炎症改变：氟西汀有限的疗效。

IF 2.5 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2026-02-01 Epub Date: 2025-12-08 DOI: 10.1016/j.pbb.2025.174143

Larysa Bondarenko , Tetiana Karatsuba , Alla Voronina , Maksim Munko , Valentina Kovalenko , Ganna Shayakhmetova

Post-traumatic stress disorder (PTSD) is increasingly recognized as a systemic disorder, with neuroendocrine, metabolic, and immune alterations accompanying its behavioral symptoms. While selective serotonin reuptake inhibitors such as fluoxetine are widely used to treat PTSD, their systemic effects during critical developmental periods remain poorly understood. Using a peripubertal rat model of PTSD-like stress, we evaluated the effects of fluoxetine administered during puberty on behavior (passive avoidance), serum biochemistry, hematology, and IL-6 levels. Assessments were conducted in two phases: shortly following the end of fluoxetine treatment and in a delayed post-treatment period. PTSD-like stress enhanced aversive memory retention, an effect attenuated by fluoxetine in the short post-treatment phase but not in the delayed period. Uric acid content in serum was increased in both PTSD and PTSD+fluoxetine groups shortly post-treatment, while LDL elevation was observed only in the delayed phase. The long-term effect of fluoxetine on serum creatinine was observed. Additional hematological alterations were observed in the delayed period. Serum IL-6 levels remained persistently elevated in PTSD group across both phases, indicating sustained inflammation with no clear effect of fluoxetine. Thus, peripubertal PTSD-like stress induces behavioral and metabolic alterations that persist beyond the acute stress period. Fluoxetine partially normalized behavior but failed to prevent long-term biochemical and hematological alterations. These highlight the systemic and time-dependent consequences of peripubertal PTSD and its pharmacological treatment, underscoring the need for longitudinal monitoring of physiological outcomes alongside recovery of behavioral phenotype.

创伤后应激障碍（PTSD）越来越被认为是一种全身性疾病，其行为症状伴随神经内分泌、代谢和免疫改变。虽然选择性5 -羟色胺再摄取抑制剂如氟西汀被广泛用于治疗创伤后应激障碍，但它们在关键发育时期的全身作用仍然知之甚少。利用青春期大鼠ptsd样应激模型，我们评估了青春期给予氟西汀对行为（被动回避）、血清生化、血液学和IL-6水平的影响。评估分两个阶段进行：氟西汀治疗结束后不久和治疗后的延迟期。ptsd样压力增强了厌恶记忆的保留，氟西汀在治疗后的短时间内减弱了这种作用，但在延迟期没有减弱。PTSD和PTSD+氟西汀组在治疗后不久血清尿酸含量均升高，而LDL仅在延迟期升高。观察氟西汀对血清肌酐的长期影响。在延迟期观察到额外的血液学改变。创伤后应激障碍组血清IL-6水平在两期均持续升高，表明持续炎症，氟西汀无明显效果。因此，青春期创伤后应激样应激诱导行为和代谢改变，持续超过急性应激期。氟西汀部分正常化行为，但未能防止长期生化和血液学改变。这些研究突出了青春期创伤后应激障碍及其药物治疗的系统性和时代性后果，强调了在行为表型恢复的同时对生理结果进行纵向监测的必要性。

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引用次数: 0

The 3,4-methylenedioxymethamphetamine (MDMA) reduces prosocial behavior in the social preference test in male and female rats 在社会偏好测试中，3,4-亚甲基二氧基甲基苯丙胺（MDMA）降低了雄性和雌性大鼠的亲社会行为。

IF 2.5 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2026-02-01 Epub Date: 2025-12-05 DOI: 10.1016/j.pbb.2025.174135

Daniel A. Palacios-Lagunas , Juan C. Hernández-Mondragón , Kjell Fuxe , Dasiel O. Borroto-Escuela , Minerva Crespo-Ramírez , Francisco Pérez-Eugenio , Miguel Pérez de la Mora

The promotion of prosocial behavior is a remarkable MDMA property. Such an effect is rather uncommon among other psychoactive substances and has been proposed to be of relevance for the potential therapeutic utility of MDMA. We aim to expand our knowledge of the prosocial effects of MDMA, considering sex and housing conditions as extra variables. To this end, housed individually or collectively, male and female Wistar rats were tested using the Social Preference paradigm.

Contrary to expectations, MDMA treatment reduced the prosocial behavior in male rats, irrespective of the housing conditions. Similar effects are observed in female rats, but only in those individually housed. Intriguingly, no MDMA social effects were observed on those female rats, which are collectively housed. Also interesting was the apparent existence of two subgroups of rats that responded differentially to the MDMA administration, suggesting that individual variations among rats may influence the degree of their response to the MDMA treatment. More work is needed to understand how differences across individuals are relevant to the behavioral effects of MDMA.

促进亲社会行为是MDMA的显著特性。这种效果在其他精神活性物质中是相当罕见的，并且已被提出与MDMA潜在的治疗效用相关。我们的目标是扩大我们对MDMA的亲社会影响的认识，考虑性别和住房条件作为额外的变量。为此，使用社会偏好范式对单独或集体饲养的雄性和雌性Wistar大鼠进行了测试。与预期相反，MDMA治疗降低了雄性大鼠的亲社会行为，与住房条件无关。在雌性大鼠身上也观察到了类似的效果，但仅限于那些单独饲养的大鼠。有趣的是，在这些集体饲养的雌性大鼠身上，没有观察到MDMA的社会效应。同样有趣的是，两组大鼠对MDMA的反应明显不同，这表明大鼠的个体差异可能会影响它们对MDMA治疗的反应程度。需要做更多的工作来了解个体之间的差异如何与MDMA的行为影响相关。

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引用次数: 0

A systematic review of ketamine's anxiolytic potential in rodent behavioral models of anxiety and PTSD 氯胺酮在啮齿动物焦虑和创伤后应激障碍行为模型中的抗焦虑潜力的系统综述。

IF 2.5 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2026-02-01 Epub Date: 2025-12-12 DOI: 10.1016/j.pbb.2025.174144

Alena Lemeshova , Kaya A. Patel , Alexander J. Bloom, Lindsay Golan, Haney Haidari, Aiman Limbada, Cherish Zhao, Jennifer A. Honeycutt

Background

Ketamine, a nonselective NMDA-receptor antagonist, is an emerging therapeutic for treatment-resistant depression and could also be a promising treatment for anxiety and post-traumatic stress disorders. However, preclinical studies in these areas lack methodological standardization, limiting clinical translatability. This review evaluates ketamine's anxiolytic potential in rodents by examining outcomes among different animal models, dosages, and treatment timing.

Methods & Results

A PubMed search of studies published up to July 21, 2025, identified 562 articles assessing ketamine's effects on anxiety and PTSD in rodent models. After applying inclusion and exclusion criteria, 35 studies were analyzed. Key methodological variables, model type, dosage, and timing were summarized to assess consistency and effectiveness across studies.

Conclusion

Current research on ketamine's anxiolytic potential in rodents is limited by inconsistent methods and inadequate sex inclusion. Evidence suggests that administering 10 to 30 mg/kg intraperitoneally and waiting ≥24 h before behavioral testing procedures produces anxiolytic effects, in deficit models. Future studies should include female subjects and standardized designs to enhance clinical translatability and relevance.

背景：氯胺酮是一种非选择性nmda受体拮抗剂，是治疗难治性抑郁症的一种新兴疗法，也可能是治疗焦虑和创伤后应激障碍的一种有希望的治疗方法。然而，这些领域的临床前研究缺乏方法标准化，限制了临床可翻译性。本综述通过检查不同动物模型、剂量和治疗时间的结果来评估氯胺酮在啮齿动物中的抗焦虑潜能。方法和结果：PubMed检索了截至2025年7月21日发表的研究，确定了562篇评估氯胺酮对啮齿动物模型焦虑和创伤后应激障碍影响的文章。应用纳入和排除标准后，对35项研究进行分析。总结了关键的方法学变量、模型类型、剂量和时间，以评估研究的一致性和有效性。结论：氯胺酮对啮齿动物抗焦虑作用的研究存在方法不统一、性别不充分等问题。有证据表明，在缺陷模型中，腹腔注射10至30 mg/kg并等待≥24 h后进行行为测试可产生抗焦虑作用。未来的研究应包括女性受试者和标准化设计，以提高临床可翻译性和相关性。

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引用次数: 0

Nicotinic acid (NA) facilitates antidepressant effects through promoting neuro-protective transcriptome in the hippocampus 烟酸（NA）通过促进海马神经保护转录组促进抗抑郁作用。

IF 2.5 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2026-02-01 Epub Date: 2025-12-29 DOI: 10.1016/j.pbb.2025.174145

Yikai Chen , Wen Ye , Wenxin Wang , Nan Miao , Yongqiang Sha , Tao Sun

Major depressive disorder (MDD) is characterized by anhedonia and cognitive deficits. In this study, we investigated the therapeutic effects of nicotinic acid (NA), a nicotinamide adenine dinucleotide⁺ (NAD⁺) precursor, in a mouse chronic restraint stress (CRS) model. Behavioral assessments revealed that NA ameliorated depressive-like behaviors, evidenced by restored sucrose preference and reduced immobility in forced swim and tail suspension tests, without affecting motor coordination in the rotarod test. Hippocampal transcriptomic analysis indicated that NA reversed stress-induced gene dysregulation, activated neuroprotective Wnt/β-catenin, cGMP–PKG, and cAMP pathways, and rescued lipid and porphyrin metabolism. In conclusion, NA likely exerts antidepressant effects by remodeling hippocampal gene networks to enhance synaptic plasticity and restore metabolic homeostasis. These findings highlight NA as a promising metabolic antidepressant and support the development of NAD⁺ precursor–based potential therapies for mood disorders.

重度抑郁症（MDD）以快感缺乏和认知缺陷为特征。在这项研究中，我们研究了烟酰胺腺嘌呤二核苷酸+ (NAD+)前体烟酸（NA）对小鼠慢性抑制应激（CRS）模型的治疗作用。行为评估显示，NA改善了抑郁样行为，在强迫游泳和悬尾测试中恢复了蔗糖偏好和减少了不动性，而在旋转杆测试中不影响运动协调。海马转录组学分析表明，NA逆转了应激诱导的基因失调，激活了神经保护性的Wnt/β-catenin、cGMP-PKG和cAMP通路，并恢复了脂质和卟啉代谢。综上所述，NA可能通过重塑海马基因网络，增强突触可塑性，恢复代谢稳态，从而发挥抗抑郁作用。这些发现强调NA是一种有前景的代谢性抗抑郁药，并支持基于NAD+前体的情绪障碍潜在治疗方法的发展。

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引用次数: 0

Simultaneous modulation of 5-HT6 and SERT by MM394: a dual-target ligand providing neuroprotection against amyloid-β toxicity, memory preservation, and alleviation of BPSD symptoms MM394同时调节5-HT6和SERT：一种双靶点配体，提供抗淀粉样蛋白-β毒性、记忆保存和减轻BPSD症状的神经保护。

IF 2.5 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2026-01-01 Epub Date: 2025-11-10 DOI: 10.1016/j.pbb.2025.174128

Agata Siwek , Monika Marcinkowska , Barbara Mordyl , Monika Głuch-Lutwin , Małgorzata Wolak , Magdalena Jastrzębska-Więsek , Natalia Wilczyńska-Zawal , Elżbieta Wyska , Katarzyna Szafrańska , Anna Wesołowska , Marcin Kołaczkowski

In addition to cognitive decline, 90 % of dementia patients experience behavioral and psychological symptoms of dementia, for which no safe and effective pharmacotherapy currently exists. Our study aimed to determine the therapeutic potential of the new dual 5-HT₆/SERT-acting ligand MM394 in the context of pro-cognitive and neuroprotective properties, as well as its effects on behavioral symptoms and mood disorders in patients diagnosed with Alzheimer's disease. We performed in vitro experiments to examine the neuroprotective and antioxidant properties of MM394, as well as in vivo studies on male rats to evaluate its pharmacokinetics and potential in behavioral modulation of memory and mood. Following this, we attempted to determine the molecular mechanism of action of the dual 5-HT₆/SERT targeting compound in ex vivo experiments using rats' hippocampus and prefrontal cortex. The results of our study in the HT-22 cell line support the potential of MM394 to target excitotoxicity and oxidative stress, which play a key role in neurodegeneration. Furthermore, the compound exhibits antidepressant-like activity in the forced swim test and counteracts the memory impairments caused by MK-801 in the novel object recognition assessment in rats. Ex vivo findings demonstrate that MM394 modulates mTOR and ERK1/2 phosphorylation in the studied brain areas and increases the level of BDNF in the hippocampus when co-administered with MK-801 in the novel object recognition test. As a result of these findings, MM394 may be useful as a therapeutic for BPSD, which should be further explored.

除了认知能力下降外，90% %的痴呆患者还会出现痴呆的行为和心理症状，目前尚无安全有效的药物治疗方法。我们的研究旨在确定新的双5-HT6/ sert作用配体MM394在促进认知和神经保护特性方面的治疗潜力，以及它对阿尔茨海默病患者行为症状和情绪障碍的影响。我们通过体外实验研究了MM394的神经保护和抗氧化特性，并在雄性大鼠体内研究了其药代动力学及其在记忆和情绪行为调节方面的潜力。在此基础上，我们利用大鼠海马和前额皮质进行离体实验，试图确定5-HT6/SERT双重靶向化合物的分子作用机制。我们在HT-22细胞系的研究结果支持MM394靶向兴奋性毒性和氧化应激的潜力，这在神经退行性变中起关键作用。此外，该化合物在强迫游泳测试中表现出抗抑郁样活性，并在新物体识别评估中抵消MK-801引起的大鼠记忆障碍。离体研究结果表明，当在新的目标识别测试中与MK-801共同使用时，MM394调节所研究脑区域的mTOR和ERK1/2磷酸化，并增加海马中BDNF的水平。由于这些发现，MM394可能是一种有用的治疗BPSD的药物，值得进一步探索。

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引用次数: 0

Noradrenergic inputs to the basolateral amygdala have bidirectional effects on coping behavior and neuronal activity in mice 基底外侧杏仁核的去肾上腺素能输入对小鼠的应对行为和神经元活动具有双向影响

IF 2.5 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2026-01-01 Epub Date: 2025-11-14 DOI: 10.1016/j.pbb.2025.174130

Alexa R. Soares , Caroline Fai , Yann S. Mineur , Marina R. Picciotto

Norepinephrine (NE) signaling is disrupted in stress disorders, with insufficient NE signaling implicated in major depressive disorder and hyperactive NE signaling associated with post-traumatic stress disorder, suggesting that adequate mood regulation requires optimal NE levels. The basolateral amygdala (BLA) is a hub for stress processing and receives dense noradrenergic innervation from the locus coeruleus (LC), the primary noradrenergic nucleus in the brain. The relationship between LC activity and cognitive/behavioral function during fear conditioning has been described as an inverted U, in which moderate LC activity, and subsequent NE release, is required for adaptive coping to threats, while hyperactive LC-NE signaling drives maladaptive behavioral responses. We used fiber photometry to measure NE signaling in the mouse BLA during acute behavioral responses to escapable and inescapable stressors, and then used an optogenetic approach to stimulate the noradrenergic terminals in the BLA at different frequencies to evaluate effects on coping behavior and cFos expression in the LC-BLA circuit. We found that low-frequency stimulation of the circuit inhibited both passive coping and BLA neuronal activity, while high-frequency stimulation had the opposite effect; the behavioral effects were not mediated by sex, but the cFos effects were specific to males. This study represents an expansion of the inverted U framework to encompass LC-BLA signaling driving acute behavioral responses to stress.

去甲肾上腺素（NE）信号在应激障碍中被破坏，NE信号不足与重度抑郁症有关，NE信号过度活跃与创伤后应激障碍有关，这表明充分的情绪调节需要最佳的NE水平。基底外侧杏仁核（BLA）是应激处理的中枢，并接受来自蓝斑核（LC）的密集去肾上腺素能神经支配，蓝斑核是大脑中主要的去肾上腺素能核。在恐惧条件反射过程中，LC活动与认知/行为功能之间的关系被描述为倒U型，其中适度的LC活动和随后的NE释放是适应性应对威胁所必需的，而过度活跃的LC-NE信号则会导致适应不良的行为反应。我们采用纤维光度法测量小鼠BLA在可逃避和不可逃避应激源的急性行为反应中的NE信号，然后采用光遗传学方法以不同频率刺激BLA的去甲肾上腺素能末端，以评估对LC-BLA回路中应对行为和cFos表达的影响。研究发现，低频刺激对被动应对和BLA神经元活动均有抑制作用，而高频刺激则相反；行为效应不受性别的影响，但cfo效应是男性特有的。这项研究代表了倒U型框架的扩展，包括LC-BLA信号驱动对压力的急性行为反应。

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引用次数: 0

Intra-accumbens melanin-concentrating hormone (MCH) receptor-1 antagonism on opioid-driven sucrose consumption in male and female rats 雄性和雌性大鼠阿片驱动的蔗糖消耗对伏隔核内黑色素浓缩激素受体-1的拮抗作用

IF 2.5 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2026-01-01 Epub Date: 2025-11-29 DOI: 10.1016/j.pbb.2025.174134

Yonca Cam , Carlos A. Sardina , Sanya K. Suri , Elizabeth C. Pickering , Felicia M. Padilla , Matthew J. Will

Melanin-concentrating hormone (MCH) system within the nucleus accumbens (Acb) has been shown to regulate feeding behavior; however, the interaction between MCH and opioid-driven hedonic eating remains unclear. This study investigated the effects of intra-Acb administration of the MCHR1 antagonist SNAP-94847 on opioid-driven sucrose pellet intake in male and female rats. Subjects received MCHR1 antagonist (N-(3-{1-[4-(3,4-difluoro-phenoxy)-benzyl]-piperdin-4-yl}-4-methyl-phenyl)-isobutyramide (SNAP-94847; 0 μg, 1.5 μg, and 15 μg/0.5 μl/side) immediately prior to intra-Acb administration of the μ-opioid receptor agonist, D-Ala2, NMe-Phe4, Glyol5-enkephalin (DAMGO; 0 μg and 0.025 μg/0.5 μl/side) before completing free-feeding tests. Results showed that DAMGO significantly increased sucrose pellet intake in both sexes, while SNAP-94847 alone had no effect, nor did it block the DAMGO-induced increase in either males or females. This finding suggests that MCHR1 within the Acb does not play a significant role in low-effort palatability-driven motivation for food consumption, contrasting with its role in effort-based motivation tasks.

伏隔核（Acb）内的黑色素浓缩激素（Melanin-concentrating hormone， MCH）系统已被证明调节摄食行为；然而，MCH与阿片类药物驱动的享乐性饮食之间的相互作用尚不清楚。本研究探讨了acb内给药MCHR1拮抗剂SNAP-94847对雄性和雌性大鼠阿片类药物驱动的蔗糖颗粒摄入的影响。受试者在完成自由喂养试验之前，立即服用MCHR1拮抗剂(N-（3-{1-[4-（3,4-二氟-苯氧基）-苄基]-胡椒丁-4-基}-4-甲基苯基）-异丁酰胺（nap -94847, 0 μg、1.5 μg和15 μg/0.5 μl/侧），然后给药μ-阿片受体激动剂D-Ala2、NMe-Phe4、glyol5 -脑啡肽（DAMGO， 0 μg和0.025 μg/0.5 μl/侧）。结果显示，DAMGO显著增加了两性蔗糖颗粒的摄入量，而单独使用SNAP-94847没有影响，也没有阻止DAMGO诱导的雄性或雌性蔗糖颗粒的增加。这一发现表明，与在基于努力的动机任务中的作用相比，Acb内的MCHR1在低努力的可口性驱动的食物消费动机中不起重要作用。

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引用次数: 0

6-Methyl nicotine and nicotine have similar thermoregulatory and reinforcing effects in middle aged female rats with a history of nicotine vapor self-administration 6-甲基尼古丁和尼古丁对有尼古丁蒸气自我服用史的中年雌性大鼠具有相似的体温调节和强化作用。

IF 2.5 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2026-01-01 Epub Date: 2025-11-14 DOI: 10.1016/j.pbb.2025.174132

Michael A. Taffe , Tyra R. Coons , Tess A. Doran , Yanabel Grant , Sophia A. Vandewater

Rationale

The nicotine analog 6-methyl nicotine (6-MN) has recently appeared in non-tobacco nicotine delivery products, including oral pouches and e-cigarette liquids, in an apparent ploy to evade regulation of nicotine by the United States Food and Drug Administration or other public health agencies. Unfortunately, only minimal scientific information on the effects of 6-MN is available.

Objective

To determine the extent to which 6-MN produces nicotine-like effects on body temperature, wheel activity and nociception in laboratory rodents.

Methods

Middle-aged (starting at Post Natal Day 425) female Wistar rats were evaluated for rectal temperature, voluntary wheel activity, and nociceptive responses (warm water tail-withdrawal) to subcutaneous injection of nicotine (0.0, 0.8 mg/kg) or 6-methyl nicotine (6-MN; 0.0, 0.4, 0.8 mg/kg). Temperature and nociceptive responses to vapor inhalation of 6-MN [0–30 mg/mL in the propylene glycol (PG) vehicle] were assessed. Finally, the self-administration of 6-MN vapor was compared with nicotine vapor self-administration.

Results

6-MN decreased rectal temperature, suppressed wheel activity and induced modest nociceptive effects. The magnitude of the effect of 0.8 mg/kg 6-MN and 0.8 mg/kg nicotine were similar across all three assays. Vapor self-administration of 6-MN and nicotine was likewise comparable at a 10 mg/mL concentration.

Conclusion

6-MN administered by injection or by vapor inhalation produces behavioral and physiological effects that are very similar to those produced by nicotine in rats. It is therefore likely that detrimental health effects of 6-MN will be quite similar to those established for nicotine.

理由：尼古丁类似物6-甲基尼古丁（6-MN）最近出现在非烟草尼古丁输送产品中，包括口服袋和电子烟液，这显然是为了逃避美国食品和药物管理局或其他公共卫生机构对尼古丁的监管。不幸的是，关于6-MN影响的科学信息很少。目的：探讨6-MN对实验鼠类体温、轮活动和伤害感受产生尼古丁样影响的程度。方法：观察中年雌性Wistar大鼠（出生后425天开始）对尼古丁（0.0、0.8 mg/kg）或6-甲基尼古丁（6-MN; 0.0、0.4、0.8 mg/kg）皮下注射的直肠温度、自主轮活动和伤害反应（温水退尾）。评估6-MN[0-30 mg/mL丙二醇（PG）载药]蒸汽吸入的温度和伤害性反应。最后，将6-MN蒸汽自给药与尼古丁蒸汽自给药进行比较。结果：6-MN降低直肠温度，抑制轮活动，并引起适度的伤害效应。0.8 mg/kg 6-MN和0.8 mg/kg尼古丁的影响程度在所有三种分析中都是相似的。6-MN和尼古丁在10 mg/mL浓度下也具有可比性。结论：6-MN通过注射或蒸汽吸入对大鼠产生的行为和生理效应与尼古丁非常相似。因此，6-MN对健康的有害影响很可能与尼古丁的有害影响非常相似。

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引用次数: 0

Dual orexin receptor antagonists in insomnia: Toward a new therapeutic paradigm 双重食欲素受体拮抗剂治疗失眠：迈向新的治疗范式。

IF 2.5 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior

Pub Date : 2026-01-01 Epub Date: 2025-10-24 DOI: 10.1016/j.pbb.2025.174117

Shigeyuki Chaki , Yumiko Imadera

Although three dual orexin receptor antagonists (DORAs), suvorexant, lemborexant, and daridorexant, are currently available and widely used to treat insomnia, the differences in their elimination half-lives are not sufficient. As a result, clinicians have limited ability to tailor therapy to individual sleep complaints. The emergence of vornorexant, with a notably short half-life comparable to that of zolpidem, may substantially expand the clinical utility of DORAs. This broader spectrum of pharmacokinetic profiles enables more individualized treatment strategies that align with patients' specific sleep complaints. This approach, in turn, potentially reshapes the therapeutic paradigm of insomnia management. However, several challenges remain to be addressed in order to fully realize the clinical potential of DORAs. This review identifies four key challenges requiring resolution to advance their optimal use in clinical practice.

虽然目前有三种双食欲素受体拮抗剂（DORAs）， suvorexant， lemborexant和daridorexant被广泛用于治疗失眠，但它们的消除半衰期的差异还不够。因此，临床医生针对个人睡眠问题量身定制治疗的能力有限。vornorexant的出现，与唑吡坦相比，其半衰期明显较短，可能会大大扩大dora的临床应用。这种更广泛的药代动力学谱使更个性化的治疗策略与患者的特定睡眠抱怨保持一致。这种方法，反过来，有可能重塑失眠管理的治疗范式。然而，为了充分发挥DORAs的临床潜力，仍有几个挑战有待解决。本综述确定了需要解决的四个关键挑战，以促进其在临床实践中的最佳应用。

引用次数: 0