Yawning elicited by intravenous ethanol in rhesus monkeys with experience self-administering cocaine and ethanol: Involvement of dopamine D3 receptors

Characterization of the effects of long-term alcohol consumption on the brain would be aided by the development of behavioral assays that are relatively easy to implement in animal models of alcohol use disorders. Assessing unconditioned behaviors, such as drug-elicited yawning in models that permit long-term alcohol ingestion, may be a valuable complement to more invasive and costly procedures. The present studies investigated previous unexpected findings of ethanol-induced yawning in nonhuman primates. Subjects were adult male rhesus monkeys (n = 8), all of which had experience self-administering intravenous cocaine for several years. Four monkeys also had experience consuming 2.0 g/kg ethanol over 1 h per day, 5 days per week, for 6.8-12.0 months. All monkeys received saline or ethanol (0.25-1.0 g/kg) infused intravenously (i.v.) over 10 min, and the number of yawns elicited during the infusion was counted. A second experiment in the ethanol-experienced monkeys examined whether ethanol-induced yawning could be blocked by PG01037 (1.0, 3.0 mg/kg, i.v.), a selective antagonist at dopamine D3 receptors (D3R). Ethanol significantly and dose-dependently increased yawns in the ethanol-experienced animals, but not the ethanol-naïve animals. In the ethanol-experienced monkeys, this effect of ethanol was blocked by the D3R antagonist. The pharmacology of yawning is complex and a good deal of model development remains to be performed to characterize the potential involvement of other neurotransmitter systems. Nonetheless, drug-elicited yawning may be a useful unconditioned behavioral assay to assess the effects of long-term alcohol consumption in established nonhuman primate models.