Neurosci. 2018 Feb 12.
Bidirectional and long-lasting control of alcohol-seeking behavior by corticostriatal LTP and LTD.
Ma T1, Cheng Y1, Roltsch Hellard E1, Wang X1, Lu J1, Gao X2, Huang CCY1, Wei XY1, Ji JY2, Wang J3.
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. Here 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
NMDA-receptor inhibition unmasked an endocannabinoid-dependent LTD. In vivo application of
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.