Administration of nicotine to adolescent rats evokes regionally selective upregulation of CNS alpha 7 nicotinic acetylcholine receptors.
Alpha 7 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 alpha 7 nAChRs in the striatum, brainstem and cerebellum. During the period of nicotine administration (30-47.5 days of age), nicotine elicited alpha 7 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 alpha 7 nAChRs were distinct from those reported earlier for the alpha 4 beta 2 subtype, and neither adult nor fetal/neonatal administration upregulates the alpha 7 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 alpha 7 nAChRs in its unique effects during this developmental period.
Slotkin
Theodore A
TA
Box 3813 DUMC, Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA. t.slotkin@duke.edu
Cousins
Mandy M
MM
Seidler
Frederic J
FJ
D000367:Age Factors; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism*; D001933:Brain Stem / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D002531:Cerebellum / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012741:Sexual Maturation; D015854:Up-Regulation / Q000187:drug effects; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579165:Chrna7 protein, rat; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D009538:Nicotine