Repeated in vivo exposure of cocaine induces long‐lasting synaptic plasticity in hypocretin/orexin‐producing neurons in the lateral hypothalamus in mice

作者：Yan Rao, Yann S. Mineur, Geliang Gan, Alex Hanxiang Wang, Zhong‐Wu Liu, Xinyuan Wu, Shigetomo Suyama, Luı́s de Lecea, Tamás L. Horváth, Marina R. Picciotto, Xiao‐Bing Gao · 发表于：The Journal of Physiology · 年份：2013 · DOI：10.1113/jphysiol.2012.246983 · 被引用次数：49 · 研究领域：Sleep and Wakefulness Research、Regulation of Appetite and Obesity、Memory and Neural Mechanisms

Key points Repeated, but not single, in vivo cocaine exposure leads to an experience‐dependent potentiation of glutamatergic synapses on hypocretin‐producing neurons (hypocretin neurons) in mice. The locus of synaptic potentiation is at the postsynaptic site of glutamatergic synapses on hypocretin neurons and the up‐regulation of AMPA‐type glutamate receptors may be involved. Cocaine‐induced synaptic potentiation is long‐lasting and exists during the abstinence of cocaine. The expression of tetanus‐induced long‐term potentiation is facilitated in hypocretin neurons in cocaine‐treated mice. These results may help us better understand the role of the hypocretin system in behavioural changes related to cocaine addiction in animals and humans. Abstract Hypocretin (orexin), a neuropeptide synthesized exclusively in the perifornical/lateral hypothalamus, is critical for drug seeking and relapse, but it is not clear how the circuitry centred on hypocretin‐producing neurons (hypocretin neurons) is modified by drugs of abuse and how changes in this circuit might alter behaviours related to drug addiction. In this study, we show that repeated, but not single, in vivo cocaine administration leads to a long‐lasting, experience‐dependent potentiation of glutamatergic synapses on hypocretin neurons in mice following a cocaine‐conditioned place preference (CPP) protocol. The synaptic potentiation occurs postsynaptically and probably involves up‐regulation of AMPA‐type glutamate receptors on...