Administration of nicotine to adolescent rats evokes regionally selective upregulation of CNS α7 nicotinic acetylcholine receptors

Abstract

α7 Nicotinic acetylcholine receptors (nAChRs) play a role in axonogenesis, synaptogenesis and synaptic plasticity, and are therefore targets for developmental neurotoxicants. We administered nicotine to adolescent rats and evaluated the effects on α7 nAChRs in the striatum, brainstem and cerebellum. During the period of nicotine administration (30–47.5 days of age), nicotine elicited α7 nAChR upregulation with a regional hierarchy of striatum>brainstem>cerebellum. Values returned to normal or became slightly subnormal almost immediately after the cessation of treatment (50 days of age) with no further changes through 75 days of age. The temporal and regional patterns of the effects on α7 nAChRs were distinct from those reported earlier for the α4β2 subtype, and neither adult nor fetal/neonatal administration upregulates the α7 subtype in the striatum. Targeting of the striatum is thus unique to nicotine exposure during adolescence and parallels earlier work showing regionally selective effects of this treatment on synaptic signaling. We obtained preliminary evidence for nicotine-induced oxidative stress as a potential contributory mechanism. The present findings reinforce the concept of biologically distinct effects of nicotine in the adolescent brain and provide evidence for a mechanistic involvement of α7 nAChRs in its unique effects during this developmental period.