Alcohol exposure disrupts mu opioid receptor-mediated long-term depression at insular cortex inputs to dorsolateral striatum

Nat Commun. 2018 Apr 3;9(1):1318. doi: 10.1038/s41467-018-03683-1.


Drugs of abuse, including alcohol, ablate the expression of specific forms of long-term synaptic depression (LTD) at glutamatergic synapses in dorsal striatum (DS), a brain region involved in goal-directed and habitual behaviors. This loss of LTD is associated with altered DS-dependent behavior. Given the role of the µ-opioid receptor (MOR) in behavioral responding for alcohol, we explored the impact of alcohol on various forms of MOR-mediated synaptic depression that we find are differentially expressed at specific DS synapses. Corticostriatal MOR-mediated LTD (mOP-LTD) in the dorsolateral striatum occurs exclusively at inputs from anterior insular cortex and is selectively disrupted by in vivo alcohol exposure. Alcohol has no effect on corticostriatal mOP-LTD in dorsomedial striatum, thalamostriatal MOR-mediated short-term depression, or mOP-LTD of cholinergic interneuron-driven glutamate release. Disrupted mOP-LTD at anterior insular cortex-dorsolateral striatum synapses may therefore be a key mechanism of alcohol-induced neuroadaptations involved in the development of alcohol use disorders.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Drinking*
  • Animals
  • Brain / pathology
  • Cerebral Cortex / metabolism*
  • Corpus Striatum / metabolism*
  • Ethanol / pharmacology
  • Genotype
  • Long-Term Potentiation
  • Long-Term Synaptic Depression / drug effects*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neostriatum / metabolism
  • Neuronal Plasticity / drug effects
  • Receptors, Cholinergic / metabolism
  • Receptors, Opioid, mu / metabolism*
  • Synapses / physiology*


  • Receptors, Cholinergic
  • Receptors, Opioid, mu
  • Ethanol