The effect of chronic administration of nicotine on antinociception, opioid receptor binding and met-enkelphalin levels in rats

The effect of chronic nicotine administration on (1) antinociception; (2) o pioid receptor binding; and (3) met-enkelphalin levels in discrete brain re gions in rats was investigated. Male and female Sprague-Dawley rats were tr eated with nicotine 0.3 mg/kg, 0.1 mg/kg, or saline three times a day subcu taneously during a 14-day protocol. Antinociception was measured by hotplat e (HP) test on days 1, 2, 7, 10 and 14. After completion of the protocol, m u-opioid receptors were analyzed by [H-3]-DAMGO binding studies and met-enk elphalin levels were determined by radioimmunoassay. Results indicated that hot-plate latency increased during the first 2 days of nicotine administra tion for male and female rats who were treated with 0.3 mg/kg nicotine. The re was an up-regulation of mu-receptors (increased B-max) in the striatum o f rats treated with 0.3 mg/kg nicotine, compared to 0.1 mg/kg nicotine and saline groups. An interaction effect of group by gender was noted. After 14 days of chronic nicotine administration, met-enkelphalin levels were signi ficantly lower in striatum and midbrain of animals treated with 0.3 mg/kg n icotine, as compared to controls. These results suggest that chronic nicoti ne administration, in doses representative of human smoking, produces antin ociception initially, and is accompanied by an upregulation of mu-opioid re ceptors in the striatum of rats. In addition, nicotine-induced tolerance to antinociception may be associated with a decrease in met-enkelphalin level over a period of time. (C) 1999 Published by Elsevier Science B.V. Al righ ts reserved.