Alcohol consumption does not impact delta and kappa opioid receptor-mediated synaptic depression in dorsolateral striatum of adult male mice.

Many drugs of abuse, including alcohol, disrupt long-term synaptic depression (LTD) at dorsal striatal glutamate synapses. This disruption is common to many forms of LTD that are mediated by G protein coupled receptors (GPCRs) that signal through the inhibitory G i/o class of G proteins. A loss of LTD is thought to mediate behavioral changes associated with the development of substance use disorders. We have previously shown in multiple studies that LTD mediated by the G i/o -coupled mu opioid receptor is disrupted by in vivo opioid and alcohol exposure in adolescent and adult mice. One of our previous studies suggested that LTD mediated by delta and kappa opioid receptors was resistant to the LTD-disrupting properties of in vivo opioid exposure. We hypothesized that delta and kappa opioid receptor-mediated LTD would be exceptions to the generalizable observation that forms of dorsal striatal G i/o -coupled receptor LTD are disrupted by drugs of abuse. Specifically, we predicted that these forms of LTD would be resistant to the deleterious effects of alcohol consumption, just as they were resistant to opioid exposure. Indeed, in adult male mice that drank alcohol for 3 weeks, delta and kappa opioid receptor-mediated LTD at glutamatergic inputs to direct pathway and indirect pathway medium spiny neurons in the dorsolateral striatum was unaffected by alcohol. These data demonstrate that alcohol effects on GPCR-mediated LTD are not generalizable across all types of G i/o -coupled GPCRs.