The Role of Orexin-1 Receptors Within the Hippocampal CA1 Area in the Extinction and Reinstatement of Methamphetamine-Seeking Behaviors

被引:0
|
作者
Ali Veisi
Hossein Khaleghzadeh‐Ahangar
Mojdeh Fattahi
Abbas Haghparast
机构
[1] Behbahan Faculty of Medical Sciences,Department of Physiology
[2] Babol University of Medical Sciences,Department of Physiology, School of Medicine
[3] Babol University of Medical Sciences,Immunoregulation Research Center, Health Research Institute
[4] Shahid Beheshti University of Medical Sciences,Neuroscience Research Center, School of Medicine
[5] Institute for Research in Fundamental Sciences,School of Cognitive Sciences
[6] Iranian Academy of Medical Sciences,Department of Basic Sciences
来源
Neurochemical Research | 2023年 / 48卷
关键词
Reward; Addiction; Methamphetamine; Orexin; Hippocampus; CA1; Conditioned place preference;
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中图分类号
学科分类号
摘要
Psychostimulant addiction is a chronic brain disorder with high relapse rates, requiring new therapeutic strategies. The orexin system is highly implicated in processing reward and addiction through connections with critical areas such as the hippocampus. This study investigated the role of orexin-1 receptors (OX1R) within the CA1 subregion of the hippocampus in the extinction and reinstatement of the methamphetamine-induced conditioned place preference. After cannulae implantation, recovery, and establishing the methamphetamine place preference, 98 male Wistar rats received different doses of bilateral intra-CA1 selective OX1R antagonist, SB334867 (1, 3, 10, and 30 nmol/0.5 μl DMSO per side) during the 10-day extinction period (daily) or after extinction phase, just on the reinstatement day (single dose) in separate experimental and control groups. The findings indicated that bilateral microinjection of SB334867 into the CA1 area during the extinction period could significantly reduce the extinction latency and maintenance of rewarding aspects of methamphetamine dose-dependently (3, 10, and 30 nmol). In another set of experiments, a single dose of bilateral intra-CA1 SB334867 administration on the reinstatement phase prevented the methamphetamine-induced reinstatement of drug-seeking behaviors at the high doses (10, and 30 nmol). The present study provided more evidence for the implication of hippocampal OX1R in the maintenance of rewarding and reinforcing properties of methamphetamine and its role in the relapse of methamphetamine-seeking behavior. Further investigations on the role of the orexin system, including the orexin-2 receptors in treating addiction, are needed to introduce its antagonists as effective therapeutic options for psychostimulant addiction.
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页码:671 / 680
页数:9
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