Peri-adolescent Alcohol Consumption Increases Sensitivity and Dopaminergic Response to Nicotine During Adulthood in Female Alcohol-preferring (P) Rats: Alterations to α7 Nicotinic Acetylcholine Receptor Expression

Adolescent alcohol drinking has been linked to increased risk for drug abuse during adulthood. Nicotine microinjected directly into the posterior ventral tegmental area (pVTA) stimulates dopamine (DA) release in the nucleus accumbens (NAc) shell. The α7 nicotinic acetylcholine receptor (nAChR) is a potent regulator of dopaminergic activity in the pVTA. The current experiments examined the effects of peri-adolescent ethanol (EtOH) drinking on the ability of intra-pVTA nicotine to stimulate DA release during adulthood and alterations in α7 nAChR expression within the pVTA. Alcohol-preferring (P) female rats consumed EtOH and/or water during adolescence (post-natal day [PND] 30-60) or adulthood (PND 90-120). Thirty days following removal of EtOH, subjects received microinjections of 1 μM, 10 μM, or 50 μM nicotine into the pVTA concurrently with microdialysis for extracellular DA in the NAc shell. Brains were harvested from an additional cohort after PND 90 for quantification of α7 nAChR within the pVTA. The results indicated that only adolescent EtOH consumption produced a leftward and upward shift in the dose response curve for nicotine to stimulate DA release in the NAc shell. Investigation of α7 nAChR expression within the pVTA revealed a significant increase in animals that consumed EtOH during adolescence compared to naïve animals. The data suggests that peri-adolescent EtOH consumption produced cross-sensitization to the effects of nicotine during adulthood. The interaction between adolescent EtOH consumption and inflated adult risk for drug dependency could be predicated, at least in part, upon alterations in α7 nAChR expression within the mesolimbic reward pathway.