Department of Neurobiology, School of Basic Medical Sciences, Key Laboratory for Neuroscience of the Ministry of Education and National Health Commission, Neuroscience Research Institute, Peking University, Beijing, China.
Department of Neurobiology, School of Basic Medical Sciences, Key Laboratory for Neuroscience of the Ministry of Education and National Health Commission, Neuroscience Research Institute, Peking University, Beijing, China.
Behav Brain Res. 2020 Feb 3;379:112365. doi: 10.1016/j.bbr.2019.112365. Epub 2019 Nov 16.
Re-exposure to drug or drug-associated cues after withdrawal can induce behavioral sensitization expression in animals or increase in the expected effect to drug in humans, which mean an enhanced drug seeking/taking motivation to trigger relapse after abstinence. The Nucleus accumbens (NAc) is known to play a key role in mediating this motivation. Recently, it has been shown that systemic administration of orexin receptor 1 (OXR1) antagonist attenuates animals' motivation behavior to take drug by self-administration paradigm, which is more effectively than orexin receptor 2 (OXR2) antagonist. However, the effect of OXR1 in the NAc on drug-induced locomotor sensitization remains elusive. The present study was designed to investigate the effect of OXR1 in the NAc on chronic cocaine-induced locomotor sensitization. Rats were given 10 mg/kg cocaine intraperitoneal injection (i.p.) for five consecutive days, followed by 10 mg/kg cocaine re-exposure (challenge) on the 14th day of withdrawal. Results showed that re-exposure to cocaine after withdrawal could induce locomotor sensitization expression in cocaine-sensitized rats. Simultaneously, the number of OXR1 positive neurons and OXR1 membrane protein level in the NAc core but not the shell were significantly increased following the cocaine re-exposure. Further, micro-infusion of SB-334867, an OXR1 selective antagonist, into the NAc core but not the shell before cocaine re-exposure, significantly attenuated the expression of locomotor sensitization in rats. The findings demonstrate that OXR1 in the NAc core partially mediates the expression of chronic cocaine-induced locomotor sensitization.
戒断后重新接触药物或与药物相关的线索会在动物中诱导行为敏化表达，或增加人类对药物的预期效果，这意味着在戒断后增强了对药物的寻求/摄入动机，从而引发复发。已知伏隔核（NAc）在介导这种动机中起着关键作用。最近，研究表明，全身性给予食欲素受体 1（OXR1）拮抗剂通过自我给药范式减弱了动物对药物的动机行为，其效果比食欲素受体 2（OXR2）拮抗剂更有效。然而，OXR1 在 NAc 中对药物诱导的运动敏化的作用仍不清楚。本研究旨在探讨 OXR1 在 NAc 中对慢性可卡因诱导的运动敏化的影响。大鼠连续 5 天腹腔注射 10mg/kg 可卡因，然后在戒断的第 14 天再次给予 10mg/kg 可卡因（挑战）。结果表明，戒断后重新接触可卡因可诱导可卡因敏化大鼠的运动敏化表达。同时，在可卡因重新暴露后，NAc 核心而非壳中的 OXR1 阳性神经元数量和 OXR1 膜蛋白水平显著增加。此外，在可卡因重新暴露前，将 OXR1 选择性拮抗剂 SB-334867 微注入 NAc 核心而非壳中，可显著减弱大鼠运动敏化的表达。这些发现表明，NAc 核心中的 OXR1 部分介导了慢性可卡因诱导的运动敏化的表达。
