Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, CT 06511, USA.
Psychopharmacology (Berl). 2013 Sep;229(1):73-82. doi: 10.1007/s00213-013-3082-0. Epub 2013 Apr 30.
Phasic dopamine (DA) signaling underlies reward learning. Cholinergic and glutamatergic inputs into the ventral tegmental area (VTA) are crucial for modulating burst firing activity and subsequent phasic DA release in the nucleus accumbens (NAc), but the specific VTA nicotinic receptor subtypes that regulate phasic DA release have not been identified.
The goal was to determine the role of VTA N-methyl-D-aspartate receptors (NMDARs) and specific subtypes of nicotinic acetylcholine receptors (nAChRs) in regulating phasic DA release in the NAc core.
Fast-scan cyclic voltammetry in anesthetized rats was combined with intra-VTA micro-infusion to evaluate the ability of glutamatergic and cholinergic drugs to modulate stimulated phasic DA release in the NAc core.
VTA NMDAR blockade with AP-5 decreased, while VTA NMDAR activation with NMDA increased NAc peak phasic DA release. Intra-VTA administration of the nonspecific nAChR antagonist mecamylamine produced a persistent decrease in phasic DA release. Infusion of the α6-selective antagonist α-conotoxin MII (α-ctx MII) produced a robust, but transient decrease in phasic DA, whereas infusion of selective doses of either the α4β2-selective antagonist, dihydro-beta-erythroidine, or the α7 antagonist, methyllycaconitine, had no effect. Co-infusion of AP-5 and α-ctx MII produced a similar phasic DA decrease as either drug alone, with no additive effect.
The results suggest that VTA α6β2 nAChRs, but not α4β2 or α7 nAChRs, regulate phasic DA release in the NAc core and that VTA α6β2 nAChRs and NMDA receptors act at a common site or target to regulate NAc phasic DA signaling.
相位多巴胺（DA）信号是奖励学习的基础。胆碱能和谷氨酸能传入腹侧被盖区（VTA）对于调节伏隔核（NAc）中的爆发放电活动和随后的相位 DA 释放至关重要，但调节相位 DA 释放的特定 VTA 烟碱型乙酰胆碱受体（nAChR）亚型尚未确定。
目的是确定 VTA N-甲基-D-天冬氨酸受体（NMDAR）和特定烟碱型乙酰胆碱受体（nAChR）亚型在调节 NAc 核心中相位 DA 释放中的作用。
在麻醉大鼠中进行快速扫描循环伏安法，结合 VTA 内微灌注，以评估谷氨酸能和胆碱能药物调节 NAc 核心中刺激相位 DA 释放的能力。
VTA NMDAR 阻断剂 AP-5 降低，而 VTA NMDAR 激活剂 NMDA 增加 NAc 峰相位 DA 释放。VTA 内给予非特异性 nAChR 拮抗剂美金刚胺可持久降低相位 DA 释放。α6-选择性拮抗剂α-芋螺毒素 MII（α-ctx MII）的输注产生了强大但短暂的相位 DA 降低，而选择性剂量的α4β2-选择性拮抗剂二氢-β-石蒜碱或α7 拮抗剂甲基藜芦碱没有影响。AP-5 和 α-ctx MII 的共输注产生的相位 DA 降低与单独使用任何一种药物相似，没有相加作用。
结果表明，VTA α6β2 nAChR，而不是 α4β2 或 α7 nAChR，调节 NAc 核心中的相位 DA 释放，并且 VTA α6β2 nAChR 和 NMDA 受体在调节 NAc 相位 DA 信号的共同部位或靶点起作用。
