Effects of chronic cocaine and ethanol self‐administration on brain dopamine receptors in a rhesus monkey model of polysubstance abuse. (11th August 2022) - Say, Felicity M.
Abstract: Most individuals with cocaine use disorder also use alcohol; however, little is known about the behavioural and pharmacological mechanisms that promote co‐abuse. For example, although studies in humans and animals have documented that chronic use of either alcohol or cocaine alone decreases D2‐like receptor (D2R) availability, effects of co‐abuse of these substances on dopamine receptor function have not been characterized. These studies examined the effects of long‐term cocaine self‐administration in 12 male rhesus monkeys who also consumed either ethanol or an ethanol‐free solution each day ( n = 6 per group). Specifically, all monkeys self‐administered cocaine (0.1 mg/kg per injection) 5 days per week in the morning. In the afternoon, six monkeys consumed 2.0 g/kg ethanol over 1 h to model binge drinking and six monkeys drank an ethanol‐free solution. Assessment of D2R availability using positron emission tomography (PET) and [ 11 C]raclopride occurred when monkeys were drug‐naïve and again when monkeys had self‐administered approximately 400‐mg/kg cocaine. D3 R function was assessed at the same time points by determining the potency of the D3 R‐preferring agonist quinpirole to elicit yawns. Chronic cocaine self‐administration decreased D2R availability in subregions of the basal ganglia in control monkeys, but not those that also drank ethanol. In contrast, D3 R sensitivity increased significantly after chronic cocaine self‐administration in ethanol‐drinking monkeys but not controls. These results suggest that co‐use of ethanol substantially changes the effects of chronic cocaine self‐administration on dopamine receptors, specifically implicating D3 R as a target for medications in these individuals. Abstract : Two groups of rhesus monkeys self‐administered cocaine and drank either a solution that contained ethanol or a control solution. Positron emission tomography (PET imaging) and observable behaviour were used to track changes in brain dopamine D2 and D3 receptor function. Chronic ethanol drinking increased D3 receptor sensitivity while obscuring the effect of cocaine on D2 receptors.