Role of serotonin neurons in the dorsal raphe nucleus in heroin self-administration and punishment.

IF 6.6 1区医学 Q1 NEUROSCIENCES

Neuropsychopharmacology Pub Date : 2024-09-19 DOI:10.1038/s41386-024-01993-1

Chen Li, Nicholas S McCloskey, Saadet Inan, Lynn G Kirby

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引用次数: 0

Abstract

One hallmark of substance use disorder is continued drug use despite negative consequences. When drug-taking behavior is punished with aversive stimuli, i.e. footshock, rats can also be categorized into punishment-resistant or compulsive vs. punishment-sensitive or non-compulsive phenotypes. The serotonin (5-hydroxytryptamine, 5-HT) system modulates responses to both reward and punishment. The goal of the current study was to examine punishment phenotypes in heroin self-administration and to determine the role of dorsal raphe nucleus (DRN) 5-HT neurons in both basal and punished heroin self-administration. First, rats were exposed to punished heroin self-administration and neuronal excitability of DRN 5-HT neurons was compared between punishment-resistant and punishment-sensitive phenotypes using ex vivo electrophysiology. Second, DRN 5-HT neuronal activity was manipulated in vivo during basal and punished heroin self-administration using chemogenetic tools in a Tph2-iCre rat line. While rats separated into punishment-resistant and punishment-sensitive phenotypes for punished heroin self-administration, DRN 5-HT neuronal excitability did not differ between the phenotypes. While chemogenetic inhibition of DRN 5-HT neurons was without effect, chemogenetic activation of DRN 5-HT neurons increased both basal and punished heroin self-administration selectively in punishment-resistant animals. Additionally, the responsiveness to chemogenetic activation of DRN 5-HT neurons in basal self-administration and motivation for heroin in progressive ratio each predicted resistance to punishment. Therefore, our data support the role for the DRN 5-HT system in compulsive heroin self-administration.

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背侧剑突核5-羟色胺神经元在海洛因自我给药和惩罚中的作用

药物使用障碍的特征之一是不顾负面影响继续使用药物。当吸食毒品的行为受到厌恶刺激（如脚震）的惩罚时，大鼠也可被分为惩罚抗性或强迫性表型与惩罚敏感性或非强迫性表型。血清素（5-羟色胺，5-HT）系统可调节对奖赏和惩罚的反应。本研究的目的是检测海洛因自我给药中的惩罚表型，并确定背侧剑突核（DRN）5-HT神经元在基础和惩罚性海洛因自我给药中的作用。首先，让大鼠接受惩罚性海洛因自我给药，并使用体外电生理学方法比较DRN 5-HT神经元的神经元兴奋性，以区分惩罚抗性表型和惩罚敏感性表型。其次，在Tph2-iCre大鼠品系中使用化学遗传学工具，在基础和惩罚性海洛因自我给药期间对DRN 5-HT神经元的活性进行了体内操作。虽然大鼠对惩罚性海洛因自我给药分为惩罚抗性表型和惩罚敏感表型，但这两种表型的DRN 5-HT神经元兴奋性并无差异。对DRN 5-HT神经元的化学抑制没有效果，而对DRN 5-HT神经元的化学激活则选择性地增加了耐受惩罚动物的基础和受惩罚海洛因自我给药量。此外，DRN 5-HT 神经元在基础自我给药中对化学激活的反应性和对海洛因的动机的渐进比例都预测了对惩罚的抵抗力。因此，我们的数据支持 DRN 5-HT 系统在强迫性海洛因自我给药中的作用。

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

Neuropsychopharmacology 医学-精神病学

CiteScore

15.00

自引率

2.60%

发文量

240

审稿时长

2 months

期刊介绍： Neuropsychopharmacology is a reputable international scientific journal that serves as the official publication of the American College of Neuropsychopharmacology (ACNP). The journal's primary focus is on research that enhances our knowledge of the brain and behavior, with a particular emphasis on the molecular, cellular, physiological, and psychological aspects of substances that affect the central nervous system (CNS). It also aims to identify new molecular targets for the development of future drugs. The journal prioritizes original research reports, but it also welcomes mini-reviews and perspectives, which are often solicited by the editorial office. These types of articles provide valuable insights and syntheses of current research trends and future directions in the field of neuroscience and pharmacology.