Aberrant synaptic plasticity and alcohol addiction
作者单位：School of Pharmacy Nanjing Medical University
会议名称：《中国毒理学会第九次全国毒理学大会》
会议日期：2019年
学科分类：1002[医学-临床医学] 100205[医学-精神病与精神卫生学] 10[医学]
关 键 词：Alcohol addiction LTP LTD NMDAR Neural Circuits
摘 要：Addiction is proposed to arise from alterations in synaptic strength via mechanisms of long-term potentiation（LTP） and depression（LTD）. However, the causality between these synaptic processes and addictive behaviors is difficult to demonstrate. We report that LTP and LTD induction altered operant alcohol self-administration, a motivated drug-seeking behavior. We first induced LTP by pairing presynaptic glutamatergic stimulation with optogenetic postsynaptic depolarization in the dorsomedial striatum, a brain region known to control goal-directed behavior. Blockade of this LTP by NMDAreceptor inhibition unmasked an endocannabinoid-dependent LTD. In vivo application of the LTP-inducing protocol caused a long-lasting increase in alcohol-seeking behavior, while the LTD protocol decreased this behavior. We further identified that optogenetic LTP and LTD induction at cortical inputs onto striatal dopamine D1 receptor-expressing neurons controlled these behavioral changes. Our results demonstrate a causal link between synaptic plasticity and alcohol-seeking behavior and suggest that modulation of this plasticity may inspire a therapeutic strategy for addiction.