Rodd-Henricks Zachary A, McKinzie David L, Li Ting-Kai, Murphy James M, McBride William J
Institute of Psychiatric Research and Department of Psychiatry, Indiana University School of Medicine, Indianapolis, Indiana 46202-4887, USA.
J Pharmacol Exp Ther. 2002 Dec;303(3):1216-26. doi: 10.1124/jpet.102.038950.
The rewarding properties of cocaine have been postulated to be regulated, in part, by the mesolimbic dopamine system. However, the possibility that the rewarding properties of cocaine are mediated by direct activation of this system has yielded contradictory findings. The intracranial self-administration technique is used to identify specific brain regions involved in the initiation of response-contingent behaviors for the delivery of a reinforcer. The present study assessed whether adult Wistar rats would self-administer cocaine directly into the nucleus accumbens shell (AcbSh) and core (AcbC). For each subregion, subjects were placed in standard two-lever operant chambers and randomly assigned to one of five groups for each site that were given either artificial cerebrospinal fluid (aCSF), or 400, 800, 1200, or 1600 pmol of cocaine/100 nl to self-administer. The data indicate that rats with placements within the AcbSh readily self-administered 800 to 1600 pmol of cocaine/100 nl and responded significantly more on the active than inactive lever. These subjects also decreased responding on the active lever when aCSF was substituted for cocaine and reinstated responding on the active lever when cocaine was reintroduced. Coinfusion of the D2-like receptor antagonist sulpiride inhibited cocaine self-infusion in the AcbSh. In contrast to the AcbSh data, rats failed to self-administer any tested dose of cocaine into the AcbC or areas ventral to the AcbSh. These findings suggest that the AcbSh is a neuroanatomical substrate for the reinforcing effects of cocaine and that activation of D2-like receptors is involved.
可卡因的奖赏特性被假定部分受中脑边缘多巴胺系统调控。然而，可卡因的奖赏特性由该系统直接激活介导这一可能性却产生了相互矛盾的研究结果。颅内自我给药技术用于确定参与启动依赖反应行为以获得强化物的特定脑区。本研究评估成年Wistar大鼠是否会将可卡因直接自我注射到伏隔核壳（AcbSh）和核心（AcbC）。对于每个亚区，将实验对象置于标准的双杠杆操作性条件反射箱中，并随机分配到五个组中的一组，每组针对每个部位给予人工脑脊液（aCSF），或400、800、1200或1600 pmol的可卡因/100 nl进行自我给药。数据表明，将注射部位置于AcbSh内的大鼠很容易自我注射800至1600 pmol的可卡因/100 nl，并且在活动杠杆上的反应明显多于非活动杠杆。当用aCSF替代可卡因时，这些实验对象在活动杠杆上的反应也减少，而当重新引入可卡因时，在活动杠杆上的反应又恢复。共同注射D2样受体拮抗剂舒必利可抑制AcbSh内的可卡因自我注射。与AcbSh的数据相反，大鼠未能将任何测试剂量的可卡因自我注射到AcbC或AcbSh腹侧区域。这些发现表明，AcbSh是可卡因强化作用的神经解剖学底物，并且D2样受体的激活参与其中。
