Adolescent nicotine exposure causes persistent upregulation of nicotinic cholinergic receptors in rat brain regions

Whereas numerous studies have explored the consequences of fetal or adult n icotine exposure, little or no basic research has been conducted for nicoti ne exposure during adolescence, the developmental period in which regular c igarette use typically begins. We administered nicotine to adolescent rats on postnatal days 30-47 via continuous infusion with implanted osmotic mini pumps, using a dose rate (3-6 mg kg(-1) day(-1)) set to achieve plasma nico tine levels found in smokers; results were compared to exposure of adult ra ts. During and after exposure, we assessed nicotinic cholinergic receptor b inding in the midbrain, cerebral cortex, and hippocampus, using [H-3]cytisi ne. Robust receptor upregulation was observed with both adolescent and adul t nicotine exposure but there were major differences in the regional specif icity and persistence of effect. In adolescents, upregulation was uniform a cross all regions during the infusion period, whereas in adults, there was a distinct regional hierarchy: midbrain < cerebral cortex < hippocampus; ac cordingly, receptors in the adolescent midbrain were upregulated far more t han with adult exposure. In addition, adolescent nicotine treatment produce d long-lasting effects on the receptors, with significant increases still a pparent in male rats 1 month after the termination of drug exposure. We als o obtained evidence for hippocampal cell damage in adolescent female rats e xposed to nicotine, characterized by increases in total membrane protein co ncentration indicative of a decrease in overall cell size. Adolescent nicot ine exposure thus elicits ngion- and gender-selective effects that differ s ubstantially from those in adults, effects that may contribute to increased addictive properties and lasting deficits in behavioral performance. (C) 1 999 Elsevier Science B.V. All rights reserved.