Abstract：
Administration of cocaine increases synaptic dopamine levels by blocking dopamine reuptake and leads to increased locomotor activity and compulsive drug-seeking behaviour. It has been suggested that the lateral hypothalamus (LH) or lateral habenula (LHb) is involved in drug-seeking behaviours. To explore the role of the LH and the LHb in cocaine-induced psychomotor responses, we tested whether modulation of the LH or the LH-LHb circuit affects cocaine-induced locomotion. Cocaine-induced locomotor activity and dopamine release were suppressed by the activation of the LH with 2-[2,6-difluoro-4-[[2-[(phenylsulfonyl)amino]ethyl]thio]phenoxy]acetamide (PEPA), an AMPA receptor agonist. When the LH was inhibited by microinjection of a GABA receptor agonists mixture prior to cocaine injection, the cocaine\'s effects were enhanced. Furthermore, optogenetic activation of the LH-LHb circuit attenuated the cocaine-induced locomotion, while optogenetic inhibition of the LH-LHb circuit increased it. In vivo extracellular recording found that the LH sent a glutamatergic projection to the LHb. These findings suggest that the LH glutamatergic projection to the LHb plays an active role in the modulation of cocaine-induced psychomotor responses.
摘要：
可卡因的施用通过阻断多巴胺再摄取来增加突触多巴胺水平，并导致运动活动增加和强迫性药物寻求行为。有人建议下丘脑外侧（LH）或下丘脑外侧（LHb）参与药物寻求行为。探讨LH和LHb在可卡因诱导的精神运动反应中的作用,我们测试了LH或LH-LHb回路的调节是否会影响可卡因诱导的运动。用2-[2,6-二氟-4-[[2-[（苯磺酰基）氨基]乙基]硫代]苯氧基]乙酰胺（PEPA）激活LH，抑制了可卡因诱导的运动活性和多巴胺释放，AMPA受体激动剂。当在注射可卡因之前通过微量注射GABA受体激动剂混合物抑制LH时，可卡因的作用增强了。此外，LH-LHb回路的光遗传学激活减弱了可卡因诱导的运动，而LH-LHb回路的光遗传学抑制增加了它。体内细胞外记录发现，LH向LHb发送了谷氨酸能投射。这些发现表明，LH谷氨酸能投射到LHb在调节可卡因诱导的精神运动反应中起着积极作用。
