Melanin-concentrating hormone receptor antagonism differentially attenuates nicotine experience-dependent locomotor behavior in female and male rats

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES Pharmacology Biochemistry and Behavior Pub Date : 2023-10-02 DOI:10.1016/j.pbb.2023.173649

Isabel R.K. Kuebler , Youxi Liu , Bárbara S. Bueno Álvarez , Noah M. Huber , Joshua A. Jolton , Raaga Dasari , Ken T. Wakabayashi

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Abstract

Nicotine is a significant public health concern because it is the primary pharmacological agent in tobacco use disorder. One neural system that has been implicated in the symptoms of several substance use disorders is the melanin-concentrating hormone (MCH) system. MCH regulates various motivated behaviors depending on sex, yet little is known of how this interaction affects experience with drugs of abuse, particularly nicotine. The goal of this study was to determine the effect of MCH receptor antagonism on experience-dependent nicotine-induced locomotion after chronic exposure, particularly on the expression of locomotor sensitization. Adult female and male Wistar rats were given saline then cumulative doses of nicotine (0.1, 0.32, 0.56, and 1.0 mg/kg) intraperitoneally to determine the acute effects of nicotine (day 1). Next, rats were treated with 1.0 mg/kg nicotine for 6 days, given an identical series of cumulative doses (day 8), and then kept in a drug-free state for 6 days. On day 15, rats were pretreated with vehicle or the MCH receptor antagonist GW803430 (10 or 30 mg/kg) before another series of cumulative doses to assess response to chronic nicotine. After vehicle, male rats increased nicotine locomotor activation from day 1 to day 15, and both sexes showed a sensitized response when normalized to saline. The lower dose of GW803430 decreased locomotion compared to vehicle in females, while the higher dose decreased locomotion in males. Both sexes showed nicotine dose-dependent effects of GW803430, strongest at lower doses of nicotine. Controlling for sex-based locomotor differences revealed that females are more sensitive to GW803430. The high dose of GW803430 also decreased saline locomotion in males. Together, the results of our study suggest that MCH is involved in the expression of nicotine locomotor sensitization, and that MCH regulates these nicotine behavioral symptoms differently across sex.

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黑色素浓缩激素受体拮抗作用不同程度地减弱雌性和雄性大鼠的尼古丁体验依赖性运动行为。

尼古丁是一个重要的公共卫生问题，因为它是烟草使用障碍的主要药物。与几种物质使用障碍症状有关的一个神经系统是黑色素浓缩激素（MCH）系统。MCH根据性别调节各种动机行为，但人们对这种相互作用如何影响滥用药物的体验知之甚少，尤其是尼古丁。本研究的目的是确定MCH受体拮抗剂对慢性暴露后经验依赖性尼古丁诱导的运动的影响，特别是对运动增敏的表达的影响。对成年雌性和雄性Wistar大鼠给予生理盐水，然后腹膜内累积剂量的尼古丁（0.1、0.32、0.56和1.0mg/kg），以确定尼古丁的急性作用（第1天）。接下来，用1.0mg/kg尼古丁治疗大鼠6天，给予相同系列的累积剂量（第8天），然后在无药物状态下保持6天。在第15天，在另一系列累积剂量之前，用载体或MCH受体拮抗剂GW803430（10或30mg/kg）预处理大鼠，以评估对慢性尼古丁的反应。赋形剂后，雄性大鼠在第1天至第15天增加了尼古丁运动激活，当生理盐水正常化时，两性都表现出致敏反应。与载体相比，较低剂量的GW803430降低了雌性的运动，而较高剂量降低了雄性的运动。两性都表现出GW803430的尼古丁剂量依赖性效应，在较低剂量的尼古丁下最强。控制基于性别的运动差异表明，女性对GW803430更敏感。高剂量的GW803430也降低了雄性生理盐水的运动。总之，我们的研究结果表明，MCH参与了尼古丁运动致敏的表达，并且MCH对这些尼古丁行为症状的调节在不同性别之间是不同的。

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来源期刊

Pharmacology Biochemistry and Behavior 医学-行为科学

CiteScore

6.40

自引率

2.80%

发文量

122

审稿时长

38 days

期刊介绍： Pharmacology Biochemistry & Behavior publishes original reports in the areas of pharmacology and biochemistry in which the primary emphasis and theoretical context are behavioral. Contributions may involve clinical, preclinical, or basic research. Purely biochemical or toxicology studies will not be published. Papers describing the behavioral effects of novel drugs in models of psychiatric, neurological and cognitive disorders, and central pain must include a positive control unless the paper is on a disease where such a drug is not available yet. Papers focusing on physiological processes (e.g., peripheral pain mechanisms, body temperature regulation, seizure activity) are not accepted as we would like to retain the focus of Pharmacology Biochemistry & Behavior on behavior and its interaction with the biochemistry and neurochemistry of the central nervous system. Papers describing the effects of plant materials are generally not considered, unless the active ingredients are studied, the extraction method is well described, the doses tested are known, and clear and definite experimental evidence on the mechanism of action of the active ingredients is provided.