Abstract
The present study conducted a comprehensive examination of the putative sex differences in the potency of nicotine between male and female ICR mice using several pharmacological and behavioral tests. Among the responses to nicotine where significant sex differences were observed are the antinociceptive and the anxiolytic effects of nicotine. Female mice were found less sensitive to the acute effects of nicotine in these tests after s.c. administration. Similar gender differences were found after i.t. injection. Influence of gonadal hormones could underlie sex differences observed in our studies. Indeed, our data clearly indicate that sex hormones can modulate the effects of nicotine and nicotinic receptors in a differential manner. Progesterone and 17β-estradiol were found to block nicotine's antinociception in mice. Testosterone failed to do so. In addition, progesterone and 17β-estradiol blocked nicotine activation of α4β2 neuronal acetylcholine nicotinic receptors expressed in oocytes. Our findings contribute to our search for receptor mechanisms in drug dependence and in the discovery of better pharmacological agents for nicotine dependence.
Footnotes
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Send reprint requests to: Dr. M. Imad Damaj, Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Box 980613, Richmond, VA 23298-0613. E-mail:mdamaj{at}hsc.vcu.edu
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This work was supported by National Institute on Drug Abuse Grant DA-05274.
- Abbreviations:
- nAChR
- acetylcholine nicotinic receptor
- %MPE
- percentage maximum possible effect
- i.t.
- intrathecal
- CL
- confidence limit
- AD50
- antagonist dose 50%
- ACh
- acetylcholine
- Received April 12, 2000.
- Accepted September 10, 2000.
- The American Society for Pharmacology and Experimental Therapeutics
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