The rostromedial tegmental nucleus also referred to as the tail of the ventral tegmental area (tVTA) contains a cluster of gamma-aminobutyric acid (GABA)ergic neurons that receive dense glutamatergic afferents from the lateral habenula (LHb), and project to dopamine (DA) neurons of the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). In light of previous evidence implicating glutamate transmission in the regulation of midbrain DA neuronal activity, we first assessed the impact of intra-tVTA microinjection of NBQX (0.8 nmol/side) and PPPA (0.825 nmol/side), respectively AMPA and NMDA receptor antagonists, on reward induced by intracranial self-stimulation (ICSS) and on locomotor activity. Since the tVTA contains a large concentration of mu opioid receptors, additional measures were obtained following microinjection of endomorphin-1 (EM-1, 1 nmol/side) to confirm tVTA placements. Then, using small interfering RNAs (siRNAs), we tested the effect of tVTA downregulation of the GluN1 subunit of the NMDA receptor on reward and locomotor activity. Results show that NBQX, PPPA and EM-1 all enhance reward and locomotor activity, effects that were of different magnitude in rostral and intermediate parts of the tVTA. On the other hand, a reduction in GluN1 subunits used a marked decrease in operant responding for ICSS, but failed to alter ICSS reward and the reward-enhancing effect of PPPA. Our results support a role for the tVTA as a main inhibitory component of DA-dependent behavioral measures, and suggest that tVTA NMDA receptors that modulate reward are most likely expressed on tVTA afferent terminals.

Rostromedial 被盖核也称为腹侧被盖区的尾部 (tVTA) 包含一组 γ-氨基丁酸 (GABA) 能神经元，这些神经元接收来自外侧缰核 (LHb) 的密集谷氨酸能传入，并投射到多巴胺 (DA) ) 腹侧被盖区 (VTA) 和黑质致密部 (SNc) 的神经元。鉴于之前的证据表明谷氨酸传递参与中脑 DA 神经元活动的调节，我们首先评估了 NBQX（0.8 nmol/侧）和 PPPA（0.825 nmol/侧），分别是 AMPA 和 NMDA 受体拮抗剂的 tVTA 内显微注射的影响，关于颅内自我刺激（ICSS）和运动活动诱导的奖励。由于 tVTA 含有大量的 μ 阿片受体，在显微注射内吗啡肽-1（EM-1，1 nmol/侧）以确认 tVTA 放置后，获得了额外的测量值。然后，使用小干扰 RNA (siRNA)，我们测试了 tVTA 下调 NMDA 受体的 GluN1 亚基对奖励和运动活动的影响。结果表明，NBQX、PPPA 和 EM-1 都增强了奖励和运动活动，这些影响在 tVTA 的嘴部和中间部分具有不同程度的影响。另一方面，GluN1 亚基的减少显着降低了 ICSS 的操作响应，但未能改变 ICSS 奖励和 PPPA 的奖励增强效果。我们的结果支持 tVTA 作为 DA 依赖性行为测量的主要抑制成分的作用，并表明调节奖励的 tVTA NMDA 受体最有可能在 tVTA 传入终端上表达。