Regulation of α4β2α5 nicotinic acetylcholinergic receptors in rat cerebral cortex in early and late adolescence: Sex differences in response to chronic nicotine.
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.
Department of Pharmacology and Physiology, The George Washington University, 2300 Eye Street NW, Washington, DC, 20037, USA. Electronic address: hoegberg@gwmail.gwu.edu.
Bethany G
BG
Hoegberg
Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, 55099, Mainz, Germany. Electronic address: lomazzo@uni-mainz.de.
Ermelinda
E
Lomazzo
Department of Pharmacology and Physiology, The George Washington University, 2300 Eye Street NW, Washington, DC, 20037, USA. Electronic address: nhlee@gwu.edu.
Norman H
NH
Lee
Department of Pharmacology and Physiology, The George Washington University, 2300 Eye Street NW, Washington, DC, 20037, USA. Electronic address: dcperry48@gmail.com.
David C
DC
Perry
D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002540:Cerebral Cortex / Q000187:drug effects* / Q000254:growth & development* / Q000502:physiology; D005260:Female; D047468:Immunoprecipitation; D008297:Male; D009538:Nicotine / Q000633:toxicity; D018722:Nicotinic Agonists / Q000633:toxicity*; D011725:Pyridines; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012727:Sex Characteristics; D014316:Tritium; D015854:Up-Regulation / Q000187:drug effects
D019086:Bridged Bicyclo Compounds, Heterocyclic; C499978:Chrna5 protein, rat; D018722:Nicotinic Agonists; D011725:Pyridines; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2; D014316:Tritium; D009538:Nicotine; C082748:epibatidine
Adolescence; Chronic nicotine; Immunoprecipitation; Nicotinic receptor subtypes; α5 subunit