Neonatal nicotine administration influences ethanol-induced behaviors

Neonatal mice were administered nicotine (66 μg (−)-nicotine base/kg body weight (bw) s.c. twice daily at 0800 and 1700 h on postnatal days 10 and 14) and control mice received saline (10 ml 0.9% NaCl/kg bw s.c.) on the same occasions. Behavioral testing was initiated 3 months after birth. In Experiment 1, neonatal nicotine administration did not affect spontaneous motor activity but altered the peak dose stimulatory effect of ethanol upon locomotion and rearing activity from 3.0 mg/kg, in the control mice, to 1.5 mg/kg. Administration of the nicotine antagonist, mecamylamine (MEC, 2.0 mg/kg), had no effect upon the peak dose stimulatory effect (i.e., 1.5 mg/kg) evidenced in the nicotine-treated mice, but attenuated the stimulatory effect of the 3.0 mg/kg dose of ethanol in the control mice. In Experiment 2, the effects of neonatal nicotine administration upon ethanol intake and preference were assessed. In the single fluid access (one-bottle) test, nicotine-treated mice consumed both more ethanol (2%, 4%, or 6% concentrations) and more tap water than control mice. In the two-bottle ethanol preference test, nicotine-treated mice consumed more ethanol and tap water. Further analysis of the high-preferring (HP) ethanol mice indicated higher ethanol intake and preference in the nicotine-treated mice but no differences in tap water or total fluid intake. The present findings are considered together with prevailing notions of nicotine receptor alterations and possible cross-sensitization effects modulating substance abuse.