Hummel M, Schroeder J, Liu-Chen L-Y, Cowan A, Unterwald E M
Department of Pharmacology and the Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Neuroscience. 2006 Oct 13;142(2):481-91. doi: 10.1016/j.neuroscience.2006.06.013. Epub 2006 Aug 7.
Numerous studies support a role for the endogenous opioid system in cocaine-influenced behavior. Few of these studies, however, selectively delineate a role for the mu opioid receptor (MOR) in this regard. This investigation examined if the MOR modulates cocaine-induced behavior in mice using a 17-base antisense oligodeoxynucleotide (AS ODN) directed against the MOR coding sequence 16-32. Specifically, cocaine-induced behavioral sensitization and conditioned reward were investigated. For the sensitization study, C57BL/6J mice received eight intermittent i.c.v. infusions of saline, mismatch oligodeoxynucleotide (ODN) (20 microg/4 microl) or AS ODN (20 microg/4 microl) over 20 days. Mice also received concomitant once daily i.p. injections of saline (4 ml/kg) or cocaine (15 mg/kg) for 10 days. There was a 7-day withdrawal period, after which all mice were challenged with cocaine (15 mg/kg) to test for behavioral sensitization. For the conditioned place preference (CPP) study, mice received five i.c.v. infusions of mismatch ODN or MOR AS ODN (days 1-5). An unbiased counterbalanced conditioning procedure was used where mice were conditioned with saline (4 ml/kg, i.p.) and cocaine (15 mg/kg, i.p.) on alternate days for four sessions (days 3-6). Mice were tested on day 7 for CPP. Immediately following testing, [3H]DAMGO (D-Ala2, N-Me-Phe4, Gly-ol5-enkephalin) receptor binding to brain homogenates was conducted. MOR AS attenuated cocaine-induced behavioral sensitization and conditioned reward. MOR AS ODN also reduced [3H]DAMGO binding. Collectively, these findings implicate the MOR as playing an important neuromodulatory role in the behavioral effects of cocaine in mice.
众多研究支持内源性阿片系统在受可卡因影响的行为中发挥作用。然而，这些研究中很少有能在这方面选择性地阐明μ阿片受体（MOR）的作用。本研究使用针对MOR编码序列16 - 32的17个碱基的反义寡脱氧核苷酸（AS ODN），来检验MOR是否调节小鼠体内可卡因诱导的行为。具体而言，研究了可卡因诱导的行为敏化和条件性奖赏。在敏化研究中，C57BL / 6J小鼠在20天内接受8次间歇性脑室内注射生理盐水、错配寡脱氧核苷酸（ODN）（20微克/4微升）或AS ODN（20微克/4微升）。小鼠还在10天内每天同时腹腔注射一次生理盐水（4毫升/千克）或可卡因（15毫克/千克）。有一个7天的戒断期，之后所有小鼠用可卡因（15毫克/千克）进行激发以测试行为敏化。在条件性位置偏爱（CPP）研究中，小鼠接受5次脑室内注射错配ODN或MOR AS ODN（第1 - 5天）。采用无偏倚的平衡条件化程序，小鼠在交替的日子里用生理盐水（4毫升/千克，腹腔注射）和可卡因（15毫克/千克，腹腔注射）进行条件化，共4个时段（第3 - 6天）。在第7天对小鼠进行CPP测试。测试后立即对脑匀浆进行[3H]DAMGO（D - Ala2，N - Me - Phe4，Gly - ol5 - 脑啡肽）受体结合检测。MOR AS减弱了可卡因诱导的行为敏化和条件性奖赏。MOR AS ODN也降低了[3H]DAMGO结合。总的来说，这些发现表明MOR在可卡因对小鼠的行为影响中起着重要的神经调节作用。
