Isabel R.K. Kuebler , Youxi Liu , Bárbara S. Bueno Álvarez , Noah M. Huber , Joshua A. Jolton , Raaga Dasari , Ken T. Wakabayashi
{"title":"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。","authors":"Isabel R.K. Kuebler , Youxi Liu , Bárbara S. Bueno Álvarez , Noah M. Huber , Joshua A. Jolton , Raaga Dasari , Ken T. Wakabayashi","doi":"10.1016/j.pbb.2023.173649","DOIUrl":null,"url":null,"abstract":"<div><p><span>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 </span>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.</p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"232 ","pages":"Article 173649"},"PeriodicalIF":3.3000,"publicationDate":"2023-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Melanin-concentrating hormone receptor antagonism differentially attenuates nicotine experience-dependent locomotor behavior in female and male rats\",\"authors\":\"Isabel R.K. Kuebler , Youxi Liu , Bárbara S. Bueno Álvarez , Noah M. Huber , Joshua A. Jolton , Raaga Dasari , Ken T. Wakabayashi\",\"doi\":\"10.1016/j.pbb.2023.173649\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p><span>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 </span>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.</p></div>\",\"PeriodicalId\":19893,\"journal\":{\"name\":\"Pharmacology Biochemistry and Behavior\",\"volume\":\"232 \",\"pages\":\"Article 173649\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2023-10-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pharmacology Biochemistry and Behavior\",\"FirstCategoryId\":\"102\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0091305723001363\",\"RegionNum\":3,\"RegionCategory\":\"心理学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BEHAVIORAL SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmacology Biochemistry and Behavior","FirstCategoryId":"102","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0091305723001363","RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BEHAVIORAL SCIENCES","Score":null,"Total":0}
Melanin-concentrating hormone receptor antagonism differentially attenuates nicotine experience-dependent locomotor behavior in female and male rats
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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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.
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