Department of Pharmacology, Boston University School of Medicine, Boston, MA 02118, USA.
Eur J Pharmacol. 2011 Jan 15;650(2-3):596-604. doi: 10.1016/j.ejphar.2010.10.045. Epub 2010 Oct 27.
Muscarinic acetylcholine receptors in the nucleus accumbens play an important role in mediating the reinforcing effects of cocaine. However, there is a paucity of data regarding the role of accumbal muscarinic acetylcholine receptors in the reinstatement of cocaine-seeking behavior. The goal of these experiments was to assess the role of muscarinic acetylcholine receptors in the nucleus accumbens core and shell in cocaine and sucrose priming-induced reinstatement. Rats were initially trained to self-administer cocaine or sucrose on a fixed-ratio schedule of reinforcement. Lever-pressing behavior was then extinguished and followed by a subsequent reinstatement phase during which operant responding was induced by either a systemic injection of cocaine in cocaine-experienced rats or non-contingent delivery of sucrose pellets in subjects with a history of sucrose self-administration. Results indicated that systemic administration of the muscarinic acetylcholine receptor antagonist scopolamine (5.0 mg/kg, i.p.) dose-dependently attenuated cocaine, but not sucrose, reinstatement. Furthermore, administration of scopolamine (36.0 μg) directly into the nucleus accumbens shell or core attenuated cocaine priming-induced reinstatement. In contrast, infusion of scopolamine (36.0 μg) directly into the accumbens core, but not shell, attenuated sucrose reinstatement, which suggests that muscarinic acetylcholine receptors in these two subregions of the nucleus accumbens have differential roles in sucrose seeking. Taken together, these results indicate that cocaine priming-induced reinstatement is mediated, in part, by increased signaling through muscarinic acetylcholine receptors in the shell subregion of the nucleus accumbens. Muscarinic acetylcholine receptors in the core of the accumbens, in contrast, appear to play a more general (i.e. not cocaine specific) role in motivated behaviors.
伏隔核中的毒蕈碱乙酰胆碱受体在介导可卡因的强化效应中起着重要作用。然而，关于伏隔核中蕈碱乙酰胆碱受体在可卡因寻求行为的复发起作用的数据很少。这些实验的目的是评估伏隔核核心和壳中的蕈碱乙酰胆碱受体在可卡因和蔗糖引发的复发起作用。大鼠最初接受可卡因或蔗糖的固定比率强化训练。然后，按压行为被消除，随后进入随后的复燃阶段，在该阶段，通过给有可卡因经验的大鼠系统注射可卡因或非连续给予蔗糖丸，诱导操作性反应。结果表明，系统给予蕈碱乙酰胆碱受体拮抗剂东莨菪碱（5.0mg/kg，ip）剂量依赖性地减弱可卡因，但不减弱蔗糖的复燃。此外，将东莨菪碱（36.0μg）直接给予伏隔核壳或核内，可减弱可卡因引发的复燃。相比之下，将东莨菪碱（36.0μg）直接注入伏隔核核内，但不注入壳内，可减弱蔗糖复燃，这表明伏隔核这两个亚区的蕈碱乙酰胆碱受体在蔗糖寻求中具有不同的作用。总之，这些结果表明，可卡因引发的复燃部分是通过增加伏隔核壳亚区的毒蕈碱乙酰胆碱受体的信号传递来介导的。相比之下，伏隔核核内的蕈碱乙酰胆碱受体似乎在动机行为中发挥更普遍的作用（即不是可卡因特异性的）。
