The effects of acute and repeated nicotine doses on spontaneous activity in male and female Sprague Dawley rats: analysis of brain area epibatidine binding and cotinine levels.

Previous research in this laboratory has shown that nicotine's effects on spontaneous activity are contingent on individual differences, attenuating activity in high active rats and increasing it in low active rats. This study was designed to further evaluate this phenomenon, and to compare it with nicotine's effects on nicotinic acetylcholine receptor (nAChR) expression in several brain regions. Male and female Sprague-Dawley rats selected for differences in baseline activity were administered nicotine twice daily for 14 days, and its effects on spontaneous activity were evaluated following 1, 13 and 27 doses. Furthermore, [(3)H] epibatidine binding and plasma cotinine levels were evaluated 24 h after the 28th dose. Contrary to previous findings, the effects of repeated nicotine on spontaneous activity were minimally contingent on baseline activity levels. Following an initial attenuation, males, but not females, exhibited sensitization to nicotine's effects on spontaneous activity. [(3)H] epibatidine was significantly increased in several brain regions in both male and female nicotine-treated animals, and in females selected for high activity at baseline. However, a clear relationship between these effects and spontaneous activity was not found, due to the lack of consistent effects of nicotine administration and baseline activity on spontaneous activity. Interestingly, significant correlations suggest that rats exhibiting higher spontaneous activity on the final test day were differentially marked by higher [(3)H] epibatidine. Cotinine levels were higher in low activity males than in high activity males, but no differences were observed between high and low activity females. Thus, no clear relationship between this variable and spontaneous activity could be discerned. Based on these data, no simple relationships between the effects of nicotine administration or baseline activity on [(3)H] epibatidine binding, nicotine metabolism, or spontaneous activity were observed. However, a relationship between [(3)H] epibatidine and spontaneous activity on the final test day is suggested.