Neuronal nicotinic receptor ligands modulate chronic nicotine-induced ethanol consumption in C57BL/6J mice.

Alcohol and nicotine are commonly abused drugs in humans and evidence suggests that neuronal nicotinic acetylcholine receptors (nAChRs) in the midbrain dopamine system are common targets for the neurobehavioral interactions between alcohol (ethanol) and nicotine. The present study examined the efficacy of nAChR ligands with different pharmacological profiles such as cytisine, lobeline and dihydro-β-erythroidine (DHβE) to modulate chronic nicotine-induced increase in ethanol intake by C57BL/6J mice, using a two-bottle choice procedure. After establishment of baseline ethanol preference (10%, v/v), animals received daily subcutaneous injections of saline, nicotine (0.4 mg/kg) or different doses of cytisine, lobeline or DHβE 15 min prior to nicotine, for 10 days. Ethanol and water were presented immediately after the last (saline or nicotine) injection and fluid levels were monitored for post 1 h and 2 h treatment. Compared to control, nicotine injection significantly increased mean ethanol intake over 10 days, at both post 1 h and 2 h. Pretreatment with cytisine (0.5, 1.5 or 3.0 mg/kg) or lobeline (4.0 or 10.0 mg/kg) significantly reduced nicotine-induced increase in ethanol intake post 1 h and 2 h, without affecting water consumption. DHβE (0.5 or 2.0 mg/kg) failed to suppress nicotine-induced ethanol intake across 2 h post injection. These results indicate that nAChRmediated signaling is critical in regulating nicotine-induced ethanol drinking behaviors.