The pharmacological effects of acute ethanol on catecholamines in the medial prefrontal cortex and dorsal striatum

The dorsal striatum and the medial prefrontal cortex are part of a neurocircuitry that is affected by acute and chronic drug use. In the present studies, we sought to characterize the pharmacological effects of ethanol on extracellular catecholamine concentrations in the dorsal striatum and medial prefrontal cortex. To this end, we utilized two different routes of administration to quantify ethanol’s actions. We performed in vivo microdialysis in adult, male Long Evans rats as they received single or repeated intravenous infusions of ethanol. Following infusion of a 1-g/kg dose of ethanol, we observed no significant effects on extracellular dopamine in either the dorsomedial or dorsolateral striatum, but in a separate group of animals, we observed significant stimulation of extracellular norepinephrine in the medial prefrontal cortex. However, following a cumulative intravenous dosing protocol, we observed a gradual ramping up of tonic dopamine activity in the dorsal striatal subregions, which was more robust in the dorsomedial striatum. Subsequently, we performed in vivo microdialysis in separate groups of rats during an operant self-administration session to quantify the time course of extracellular dopamine and norepinephrine in the medial prefrontal cortex. In the seven operant sessions prior to the microdialysis test session, each group of rats had been assigned to a separate treatment group: one that received a sweetened ethanol solution, one that received a sucrose solution, and a handling control group that did not receive any drinking solutions. In the ethanol-experienced animals, we report a reduction in basal dopamine and norepinephrine in the medial prefrontal cortex, relative to control groups. However, there were no significant differences in the temporal profile of extracellular norepinephrine across the three treatment groups. These studies demonstrate that limited voluntary ethanol consumption appears to be sufficient to alter tonic catecholamine signaling in the medial prefrontal cortex. Additionally, we conclude that central catecholamine signaling pathways are a target for ethanol.