Skoubis P D, Maidment N T
Department of Psychiatry and Biobehavioral Sciences, Neuropsychiatric Institute, University of California at Los Angeles, 760 Westwood Plaza, Los Angeles, CA 90024, USA.
Neuroscience. 2003;119(1):241-9. doi: 10.1016/s0306-4522(03)00121-0.
Peripheral administration of naloxone is known to produce a conditioned place aversion and to block cocaine-induced conditioned place preference. The ventral pallidum receives a dense enkephalinergic projection from the nucleus accumbens and is implicated as a locus mediating the rewarding and reinforcing effects of psychostimulant and opiate drugs. We sought to provide evidence for the involvement of pallidal opioid receptors in modulating affective state using the place-conditioning paradigm. Microinjection of naloxone (0.01-10 microg) into the ventral pallidum once a day for 3 days dose-dependently produced a conditioned place aversion when tested in the drug-free state 24 h after the last naloxone injection. This effect was reproduced using the mu-opioid receptor selective agonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH(2) (CTOP, 1 microg). Locomotor activity was reduced following injection of the highest dose of naloxone (10 microg) but elevated following CTOP (1 microg). Daily injection of cocaine (10 mg/kg) for 3 days produced a conditioned place preference 24 h later. This effect of cocaine was attenuated by concomitant intra-ventral pallidal injection of naloxone at a dose (0.01 microg) that had no significant aversive property when injected alone. In contrast, the locomotor activation induced by peripheral cocaine injection was unaffected by naloxone injection into the ventral pallidum. The data implicate endogenous opioid peptide systems within the ventral pallidum as regulators of hedonic status.
已知外周给予纳洛酮会产生条件性位置厌恶，并阻断可卡因诱导的条件性位置偏好。腹侧苍白球接受来自伏隔核的密集脑啡肽能投射，并被认为是介导精神兴奋剂和阿片类药物奖赏和强化作用的位点。我们试图利用位置条件化范式为苍白球阿片受体参与调节情感状态提供证据。在最后一次注射纳洛酮24小时后的无药状态下进行测试时，每天一次向腹侧苍白球微量注射纳洛酮（0.01 - 10微克），持续3天，会剂量依赖性地产生条件性位置厌恶。使用μ - 阿片受体选择性激动剂D - Phe - Cys - Tyr - D - Trp - Orn - Thr - Pen - Thr - NH₂（CTOP，1微克）可重现此效应。注射最高剂量的纳洛酮（10微克）后运动活性降低，但注射CTOP（1微克）后运动活性升高。每天注射可卡因（10毫克/千克），持续3天，24小时后会产生条件性位置偏好。腹侧苍白球内同时注射单独注射时无明显厌恶特性的剂量（0.01微克）的纳洛酮，可减弱可卡因的这种效应。相反，外周注射可卡因诱导的运动激活不受向腹侧苍白球注射纳洛酮的影响。这些数据表明腹侧苍白球内的内源性阿片肽系统是享乐状态的调节因子。
