Laboratory on Neurobiology of Compulsive Behaviors, Intramural Research Program, National Institute on Alcohol Abuse and Alcoholism (NIAAA-IRP), NIH, Bethesda, MD 20892, USA.
Laboratory on Neurobiology of Compulsive Behaviors, Intramural Research Program, National Institute on Alcohol Abuse and Alcoholism (NIAAA-IRP), NIH, Bethesda, MD 20892, USA; Intramural Research Program, National Institute on Drug Abuse (NIDA-IRP), Baltimore, MD 21224, USA; Center on Compulsive Behaviors, Intramural Research Program, NIH, Bethesda, MD 20892, USA.
Cell Rep. 2018 Jun 26;23(13):3852-3863. doi: 10.1016/j.celrep.2018.05.076.
The ventral pallidum (VP) is part of the basal ganglia circuitry and a target of both direct and indirect pathway projections from the nucleus accumbens. VP is important in cocaine reinforcement, and the firing of VP neurons is modulated in vivo during cocaine self-administration. This modulation of firing is thought to be indirect via cocaine actions on dopamine in the accumbens. Here, we show that cocaine directly inhibits synaptic transmission evoked by selective stimulation of indirect pathway projections to VP neurons. The inhibition is independent of dopamine receptor activation, absent in 5-HT1B knockout mice, and mimicked by a serotonin transporter (SERT) blocker. SERT-expressing neurons in dorsal raphe project to the VP. Optogenetic stimulation of these projections evokes serotonin transients and effectively inhibits GABAergic transmission to VP neurons. This study shows that cocaine increases endogenous serotonin in the VP to suppress synaptic transmission selectively from indirect pathway projections to VP neurons.
腹侧苍白球（VP）是基底神经节回路的一部分，也是伏隔核直接和间接投射的靶点。VP 在可卡因强化中很重要，并且在可卡因自我给药过程中，VP 神经元的放电在体内被调节。这种放电的调节被认为是间接的，通过可卡因在伏隔核中对多巴胺的作用。在这里，我们表明可卡因直接抑制了选择性刺激间接通路投射到 VP 神经元的突触传递。这种抑制不依赖于多巴胺受体的激活，在 5-HT1B 敲除小鼠中不存在，并且可以被 5-羟色胺转运体（SERT）阻断剂模拟。中缝背核中的 SERT 表达神经元投射到 VP。这些投射的光遗传学刺激会引发 5-羟色胺瞬变，并有效地抑制 GABA 能传递到 VP 神经元。这项研究表明，可卡因增加了 VP 中的内源性 5-羟色胺，以选择性地抑制来自间接通路投射到 VP 神经元的突触传递。
