Adolescent and adult male rats differ in expression of three nicotinic receptor subtypes and in the response of these subtypes to chronic nicotine exposure

Abstract

Smokers who begin as adolescents have an increased likelihood of dependence to nicotine and other drugs of abuse; this may be due in part to biological differences in the response of adult and adolescent brains to nicotine. Our aim was to use quantitative autoradiography to compare expression of three subtypes of nicotinic receptor (nAChR) in brains of adolescent and adult rats, and the response of each subtype to chronic nicotine exposure. Male Sprague-Dawley rats were administered saline or nicotine (6 mg/kg/day, free base) via osmotic minipumps for 14 days, either as adolescents (PN days 29–42) or adults (PN days 69–82), and brain sections prepared for quantitative autoradiography. Adjacent sections were labeled with [125I]A-85,380 (β2∗ nAChRs), [125I]-Y0-α-conotoxin MII (α6∗ nAChRs), or [125I] α-bungarotoxin (α7 nAChRs). Binding was quantified by densitometry and compared by ANOVA. Adolescents had consistently greater binding to β2∗ nAChRs (in 17 of 23 brain regions) and α7 nAChRs (in 14 of 40 regions), but not to α6∗ nAChRs (2 of 13 regions higher). Chronic nicotine up-regulated β2∗ binding; this response was greater in adults (increased in 20 of 23 regions) than adolescents (increased in 10 of 23 regions). α7 binding was also up-regulated by nicotine, and adults also had a greater response (increased in 25 of 40 regions) than adolescents (increased in 18 of 40 regions). The α6∗ nAChRs responded differently: binding was either unchanged or decreased by nicotine, and adolescent brains were more sensitive (5 of 13 regions down-regulated) than adults (3 of 13). Adolescent rats thus differ from adults both in the expression of nAChR subtypes and in the response of these subtypes to chronic nicotine. Supported by DA015767 (DCP).