Behavioral sensitization following repeated intravenous nicotine administration: Gender differences and gonadal hormones

Repeated intermittent administration of stimulants is well known to produce behavioral sensitization in male animals. The present studies explored whe ther 1) behavioral sensitization occurred with the IV route of administrati on, 2) sensitization was greater in females than in males, 3) sensitization was modulated by gonadectomy, 4) intact adult female rats maintained norma l estrous cytology patterns in response to repeated nicotine administration , and 5) the pharmacokinetics of IV nicotine dosing. Adult male, female, ca strated, and ovariectomized Sprague-Dawley rats (n = 48) were surgically im planted with an intravenous access port. Animals received 50 mu g/kg IV nic otine once/day for 14 days. Immediately after the initial nicotine injectio n and the final day 14 nicotine injection, animals were placed in IR photoc ell activity chambers for 60 min. Observational time sampling of behavior w as also simultaneously performed by an observer blind to treatment conditio n. An increase in behavioral activity of greater than 120% occurred across the 14-day time course of IV nicotine injections. The magnitude of the incr ease, however, varied as a function of component of activity, gender, and g onadectomy. The behavioral observation data further suggested that the fema les demonstrated an increased sensitivity to repeated nicotine, as evidence d in a more rapid response, for example, grooming. These behavioral observa tions were associated with peak arterial levels of nicotine (similar to 25 ng/ml) no greater than the average venous levels of nicotine commonly maint ained by cigarette smokers. Repeated IV nicotine, at a dose of 50 mu g/kg, did not interfere with intact female vaginal cytology or body weight; the f ailure to detect such alterations were not due to inadequate statistical po wer. Moreover, no nicotine-treated animals displayed persistent vaginal est rous or were acyclic. Collectively, these data suggest that the IV nicotine model may be particularly useful in exploring the gender-dependent effects of nicotine. (C) 1999 Elsevier Science Inc.