Effects of nicotine and epibatidine on locomotor activity and conditioned place preference in rats

We studied the effects of nicotine and epibatidine given s.c. acutely and repeatedly, on locomotor activity and conditioned place preference (CPP) in rats. Nicotine at 0.5 mg/kg immediately and at 0.8 mg/kg after a delay increased the locomotor activity and its locomotor stimulant effects were greatly sensitized (about fourfold) when it was given repeatedly. Acute epibatidine at 0.6 and 3.0 μg/kg increased the activity modestly after a delay. When given repeatedly epibatidine's stimulant effects, mainly those at 3.0 μg/kg, were somewhat sensitized (less than twofold). Nicotine at 0.5 and 0.8 mg/kg produced CPP in rats in a biased paradigm. Epibatidine elicited CPP at very low dose (0.1 μg/kg), but at 0.3 or 0.6 μg/kg it induced neither preference nor aversion and at the 3.0 μg/kg dose it was aversive. Both acutely and after the repeated administration, epibatidine enhanced the locomotor activity of rats clearly less than nicotine agreeing with its previously reported lesser effects on accumbal dopamine output. Thus, while nicotine elicits CPP at doses (0.5 and 0.8 mg/kg) equal to those that increase accumbal dopamine output and locomotor activity, epibatidine seems to be aversive at the dose (3.0 μg/kg) that enhances accumbal dopamine output and increases locomotor activity.