Abstract:
The limbic system, particularly the NAc, shows a high concentration of metabotropic glutamate receptors (mGluRs). Recent evidence suggests the significant involvement of mGluRs in mental disorders, including substance abuse and addiction. The objective of this study was to examine the involvement of mGlu8 receptors in the NAc in the mechanisms underlying the extinction and reinstatement of conditioned place preference (CPP) induced by morphine. Male Wistar rats underwent surgical implantation of bilateral cannulas in the NAc and were assessed in a CPP protocol. In study 1 at the same time as the extinction phase, the rats were given varying doses of S-3,4-DCPG (0.03, 0.3, and 3 μg/0.5 μl). In study 2, rats that had undergone CPP extinction were given S-3,4-DCPG (0.03, 0.3, and 3 μg/0.5 μl) five minutes prior to receiving a subthreshold dose of morphine (1 mg/kg) in order to reactivate the previously extinguished morphine response. The findings demonstrated that administering S-3,4-DCPG directly into the accumbens nucleus resulted in a decrease in the duration of the CPP extinction phase. Moreover, dose-dependent administration of S-3,4-DCPG into the NAc inhibited CPP reinstatement. The observations imply that microinjection of S-3,4-DCPG as a potent orthosteric agonist with high selectivity for the mGlu8 receptor into the NAc promotes the process of extinction while concurrently exerting inhibitory effects on the reinstatement of morphine-induced CPP. This effect may be associated with the modulation of glutamate engagement within the NAc and the plasticity of reward pathways at the synaptic level.
摘要:
边缘系统,尤其是NAc,显示高浓度的代谢型谷氨酸受体(mGluRs)。最近的证据表明mGluRs与精神障碍有关,包括药物滥用和成瘾。这项研究的目的是研究mGlu8受体在NAc中参与吗啡诱导的条件性位置偏爱(CPP)的灭绝和恢复的机制。雄性Wistar大鼠在NAc中接受双侧插管的手术植入,并在CPP方案中进行评估。在研究1中,在灭绝阶段的同时,给予大鼠不同剂量的S-3,4-DCPG(0.03、0.3和3μg/0.5μl)。在研究2中,在接受亚阈值剂量的吗啡(lmg/kg)之前5分钟给予经历CPP消退的大鼠S-3,4-DCPG(0.03、0.3和3μg/0.5μl),以便重新激活先前熄灭的吗啡应答。研究结果表明,直接向伏隔核施用S-3,4-DCPG会导致CPP灭绝期持续时间的减少。此外,将S-3,4-DCPG剂量依赖性地给予NAc抑制CPP恢复。观察结果表明,将S-3,4-DCPG作为对mGlu8受体具有高选择性的强效正构激动剂微注射到NAc中可促进灭绝过程,同时对吗啡诱导的CPP的恢复产生抑制作用。这种作用可能与NAc内谷氨酸参与的调节以及突触水平上奖励途径的可塑性有关。