Orbitofrontal cortex subregion inhibition during binge-like and aversion-resistant alcohol drinking

Two important contributors to alcohol-related problems and alcohol use disorder (AUD) are binge- and compulsive-like drinking. The orbitofrontal cortex (OFC), a brain region implicated in outcome valuation and behavioral flexibility, is functionally altered by alcohol exposure. Data from animal models also suggest that both the medial (mOFC) and lateral (lOFC) subregions of the OFC regulate alcohol-related behaviors. The current study was designed to examine the contributions of mOFC and lOFC using a model of binge-like and aversion-resistant ethanol drinking in C57BL/6J male and female mice. The inhibitory Designer Receptor Exclusively Activated by Designer Drugs (DREADD) hM4Di were used to inhibit neurons in either the mOFC or the lOFC in mice drinking 15% ethanol in a two-bottle, limited-access, modified drinking in the dark paradigm. The effects of chemogenetic inhibition on consumption of quinine-adulterated ethanol, water, and water + quinine were also assessed. Inhibiting the mOFC did not alter consumption of ethanol or aversion-resistant drinking of ethanol + quinine. In contrast, inhibition of neurons in the lOFC increased consumption, but not preference, of ethanol alone. mOFC and lOFC inhibition did not alter water or quinine-adulterated water intake, indicating the effects shown here are specific to ethanol drinking. These data support the role of the lOFC in regulating alcohol consumption but fail to find a similar role for mOFC.