Muñoz, BraulioFritz, Brandon M.Yin, FuqinAtwood, Brady K.2018-06-142018-06-142018-04-03Muñoz, B., Fritz, B. M., Yin, F., & Atwood, B. K. (2018). Alcohol exposure disrupts mu opioid receptor-mediated long-term depression at insular cortex inputs to dorsolateral striatum. Nature Communications, 9. https://doi.org/10.1038/s41467-018-03683-12041-1723https://hdl.handle.net/1805/16505Drugs 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., µ-opioid receptors (MOR) are known to modulate the reward effects of drugs of abuse, and MOR activation induces long-term depression (LTD) at striatal synapses. Here the authors show that alcohol exposure disrupts MOR-induced LTD only at specific cortical inputs to the striatum.en-USAttribution 3.0 United StatesAlcoholDrugslong-term depressiondorsolateral striatumArticle