Effects of Nicotine on Antinociception in Male and Female Sprague- Dawley and Long-Evans Rats With and Without Stress

摘要

Nicotine, the active pharmacologic agent in tobacco, has antinociceptive effects, but the importance of individual differences and the influence of stress on nicotine-induced antinociception has not been studied previously. The present experiment examined the effects of nicotine administration on two measures of nociception in 120 Sprague-Dawley and 120 Long-Evans male and female adult rats. Two strains and both sexes were included to investigate potential genotypic and sex differences in nicotine's antinociceptive actions. Subjects received 0 (saline), 6 or 12 mg/kg/day nicotine via Alzet osmotic mini-pumps. Nociception was measured following 2, 7, and 12 days of nicotine or saline administration using hot-plate and tail-flick paradigms. Tail-flick reflects a spinally-mediated pain behavior, whereas hot- plate is believed to reflect supraspinal processes. Effects depended on the methods used to evaluate nociception, strain, sex, and time of measurement. Nicotine administration significantly increased supraspinal hot-plate latencies on day 2 such that male and female rats receiving 12 mg/kg/day had longer latencies than did saline-treated rats. Nicotine administration significantly increased spinally-mediated tail-flick latencies on day 12 such that only male Sprague-Dawley rats receiving nicotine had longer latencies than did saline controls. There were no significant effects for stress. These findings suggest that nicotine-induced supraspinal analgesia is more widely-experienced, occurs rapidly, and dissipates quickly. In contrast, spinally-mediated antinociception from nicotine takes longer to be experienced and is dependent upon genotype and sex. These findings may reflect different sensitivities to, or different effects of, nicotine on antinociception at two different levels of neural processing.