Neuropeptide cocaine- and amphetamine-regulated transcript (CART) is known to influence the activity of the canonical mesolimbic dopaminergic pathway and modulate reward seeking behaviour. CART neurons of the lateral hypothalamus (LH) send afferents to the ventral tegmental area (VTA) and paraventricular thalamic nucleus (PVT) and these nuclei, in turn, send secondary projections to nucleus accumbens. We try to dissect the precise sites of CART’s action in these circuits in promoting reward. Rats were implanted with bipolar electrode targeted at the lateral hypothalamus-medial forebrain bundle (LH-MFB) and trained to press the lever through intracranial self-stimulation (ICSS) protocol. CART (55–102) administered directly into posterior VTA (pVTA) or PVT of the conditioned rats significantly increased the number of lever presses, indicating reward-promoting activity of the peptide. Concomitant increase in dopamine (DA) and 3, 4-dihydroxyphenylacetic acid (DOPAC) efflux was noted in the microdialysate collected from the nucleus accumbens shell (AcbSh). On the other hand, immunoneutralization of endogenous CART with CART antibodies injected directly in the pVTA or PVT reduced the lever press activity as well as DA and DOPAC efflux in the AcbSh. Injection of CART (1–39) in pVTA or PVT was ineffective. We suggest that CART cells in the LH-MFB area send afferents to (a) pVTA and influence dopaminergic neurons projecting to AcbSh and (b) PVT, from where the secondary neurons may feed into the AcbSh. Excitation of the CARTergic pathway to the pVTA as well as the PVT seems to promote DA release in the AcbSh and contribute to the generation of reward.

中文翻译：

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神经肽 CART 调节伏隔核中的多巴胺周转：对奖励回路解剖的洞察

已知神经肽可卡因和苯丙胺调节的转录物 (CART) 会影响典型的中脑边缘多巴胺能通路的活性并调节奖励寻求行为。外侧下丘脑 (LH) 的 CART 神经元向腹侧被盖区 (VTA) 和室旁丘脑核 (PVT) 发送传入神经，这些核依次向伏隔核发送次级投射。我们试图剖析 CART 在这些电路中促进奖励的确切位置。大鼠被植入针对外侧下丘脑内侧前脑束 (LH-MFB) 的双极电极，并训练其通过颅内自我刺激 (ICSS) 协议按压杠杆。CART (55-102) 直接给药于条件大鼠的后部 VTA (pVTA) 或 PVT 显着增加了杠杆按压次数，表明肽的奖励促进活性。在从伏隔核壳 (AcbSh) 收集的微透析液中注意到多巴胺 (DA) 和 3, 4-二羟基苯乙酸 (DOPAC) 流出量同时增加。另一方面，用直接注射到 pVTA 或 PVT 中的 CART 抗体对内源性 CART 进行免疫中和降低了杠杆按压活动以及 AcbSh 中的 DA 和 DOPAC 流出。在 pVTA 或 PVT 中注射 CART (1-39) 是无效的。我们建议 LH-MFB 区域中的 CART 细胞向 (a) pVTA 发送传入神经，并影响投射到 AcbSh 和 (b) PVT 的多巴胺能神经元，次级神经元可以从那里馈入 AcbSh。对 pVTA 和 PVT 的 CARTergic 通路的激发似乎促进了 AcbSh 中的 DA 释放并有助于产生奖励。