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Brain Res. 1999 Mar 20;822(1-2):107-13.

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

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College of Nursing, The Ohio State University, 1585 Neil Avenue, Columbus, OH, 43210-1289, USA.


The effect of chronic nicotine administration on (1) antinociception; (2) opioid receptor binding; and (3) met-enkelphalin levels in discrete brain regions in rats was investigated. Male and female Sprague-Dawley rats were treated with nicotine 0.3 mg/kg, 0.1 mg/kg, or saline three times a day subcutaneously during a 14-day protocol. Antinociception was measured by hotplate (HP) test on days 1, 2, 7, 10 and 14. After completion of the protocol, mu-opioid receptors were analyzed by [3H]-DAMGO binding studies and met-enkelphalin levels were determined by radioimmunoassay. Results indicated that hot-plate latency increased during the first 2 days of nicotine administration for male and female rats who were treated with 0.3 mg/kg nicotine. There was an up-regulation of mu-receptors (increased Bmax) in the striatum of 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 significantly lower in striatum and midbrain of animals treated with 0.3 mg/kg nicotine, as compared to controls. These results suggest that chronic nicotine administration, in doses representative of human smoking, produces antinociception initially, and is accompanied by an upregulation of micro-opioid receptors 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.

[Indexed for MEDLINE]

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