Regulation of α4β2α5 nicotinic acetylcholinergic receptors in rat cerebral cortex in early and late adolescence: Sex differences in response to chronic nicotine

- Male rats at PN28, α4β2* nAChRs in the cortex up-regulate after chronic nicotine.
- No up-regulation of α4β2* nAChRs in female cortex at PN28 after chronic nicotine.
- Sex differences in nicotine-induced α4β2* nAChR were observed at PN42.
- No differences were observed in α5-containing nAChRs at any age or in either sex.
- Both age and sex play a role in α4β2* nAChR regulation in the cortex of rats.

Chronic nicotine administration in animals, and smoking in humans, causes up-regulation of α4β2* neuronal nicotinic receptors (nAChRs), which has been hypothesized to contribute to the addictive actions of nicotine. We used a rat model to test whether such up-regulatory effects differ in adolescents versus adults, and in males versus females. Following chronic treatment with nicotine or saline via subcutaneous osmotic minipumps, we measured α4β2 and α4β2α5 nAChRs in cerebral cortex using [3H]epibatidine to label assembled nAChRs, and selective antibodies to measure the individual subunits via immunoprecipitation. For the first time, we provide a detailed characterization of the response of both α4β2 and α4β2α5 nAChRs in female adolescent rat cerebral cortex. We found differences in nicotine-induced up-regulation between males and females in early adolescence that are absent in both late adolescence and adulthood. Males showed significant up-regulation at PN28 which was absent in age-matched females. These results demonstrate sex differences in the susceptibility of α4β2* nAChRs to the effects of chronic nicotine exposure in the cerebral cortex based on age.