Neuropeptide S system mediates nicotine-induced reward-facilitatory behavior

IF 4.6 2区医学 Q1 NEUROSCIENCES

Neuropharmacology Pub Date : 2025-06-02 DOI:10.1016/j.neuropharm.2025.110543

Harish M. Kawade , Utkarsh P. Patil , Deepali M. Pandhare , Nishikant K. Subhedar , Dadasaheb M. Kokare

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Abstract

Neuropeptide S (NPS), a 20-amino acid bioactive molecule has emerged as a promising treatment target for substance abuse in preclinical research. However, its role in nicotine reward, a major contributor to tobacco addiction, remains unexplored. This study investigated the involvement of the NPS system in reward-related effects of nicotine using the intracranial self-stimulation (ICSS) procedure in operant chamber. Adult male Wistar rats were implanted with bipolar electrode targeting the lateral hypothalamus-medial forebrain bundle and trained under a fixed-ratio 1 schedule across a range of brain stimulation frequencies (165-33 Hz). Under control conditions, the trained rats displayed a frequency-dependent increase in lever-press activity. Intracerebroventricular (i.c.v.) infusion of NPS (0.5–2 nmol) facilitated ICSS behaviour, while NPS receptor antagonist SHA-68 (0.1–10 nmol) was not effective. However, SHA-68 pretreatment (i.c.v.) dose dependently blocked the ICSS-facilitatory action of nicotine (0.25 mg/kg; subcutaneous, s.c.). A single nicotine injection (s.c.) activated NPS-containing neurons in the pericoerulear area (peri-LC), and increased NPS protein levels in the lateral hypothalamus (LH). Repeated nicotine administration (s.c.) elevated NPS mRNA expression in the peri-LC, and increased protein levels in the LH, paraventricular thalamus and peri-LC. However, these changes seem region specific since the nicotine treatment, in single or multiple doses, ensued no response in parabrachial nucleus, amygdala or ventral tegmental area. In sum, we suggest that the endogenous NPS system plays a critical role in reward-related effects of nicotine.

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神经肽S系统介导尼古丁诱导的奖励促进行为

神经肽S （Neuropeptide S， NPS）是一种由20个氨基酸组成的生物活性分子，在药物滥用的临床前研究中成为一种有前景的治疗靶点。然而，它在尼古丁奖励中的作用仍未被探索，尼古丁奖励是烟草成瘾的主要原因。本研究在手术室内采用颅内自我刺激（ICSS）方法研究了NPS系统参与尼古丁的奖赏相关效应。在成年雄性Wistar大鼠的下丘脑外侧-前脑内侧束植入双极电极，并在固定比例1的计划下进行脑刺激频率范围（165-33 Hz）的训练。在控制条件下，受过训练的大鼠在杠杆按压活动中表现出频率依赖的增加。脑室内注射NPS （0.5-2 nmol）促进ICSS行为，而NPS受体拮抗剂SHA-68 （0.1-10 nmol）无效。然而，SHA-68预处理（iccv）剂量依赖性地阻断了尼古丁(0.25 mg/kg；皮下,南卡罗来纳州)。单次尼古丁注射（s.c）激活核周区（peril - lc）含有NPS的神经元，并增加下丘脑外侧（LH） NPS蛋白水平。反复给药尼古丁（s.c）升高了lhc周围NPS mRNA的表达，并增加了LH、室旁丘脑和lhc周围的蛋白水平。然而，这些变化似乎是区域特异性的，因为单剂量或多剂量的尼古丁治疗在臂旁核、杏仁核或腹侧被盖区没有反应。总之，我们认为内源性NPS系统在尼古丁的奖励相关效应中起着关键作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neuropharmacology 医学-神经科学

CiteScore

10.00

自引率

4.30%

发文量

288

审稿时长

45 days

期刊介绍： Neuropharmacology publishes high quality, original research and review articles within the discipline of neuroscience, especially articles with a neuropharmacological component. However, papers within any area of neuroscience will be considered. The journal does not usually accept clinical research, although preclinical neuropharmacological studies in humans may be considered. The journal only considers submissions in which the chemical structures and compositions of experimental agents are readily available in the literature or disclosed by the authors in the submitted manuscript. Only in exceptional circumstances will natural products be considered, and then only if the preparation is well defined by scientific means. Neuropharmacology publishes articles of any length (original research and reviews).