Effects of nicotine exposure on locomotor activity and pCREB levels in the ventral striatum of adolescent rats.
Behavioral reactivity to novel stimuli, which is greater in the adolescent than young adult population, is associated with drug abuse liability, suggesting that the increased addiction vulnerability of adolescents may be related to heightened novel stimulus reactivity and underlying cellular processes. We examined the hypothesis that adolescent animals who exhibit higher novel stimulus reactivity, exhibit greater locomotor activity in response to nicotine than adolescents who exhibit lower novel stimulus reactivity, and that this difference is associated with alterations in CREB expression and activity in the ventral striatum (vStr) and prefrontal cortex (PFC). Adolescents exhibiting high locomotor activity (HLA) in the novel open field developed tolerance to the locomotor depressant effects of nicotine with fewer exposures and at lower doses than adolescents with low locomotor activity (LLA). Further, HLA adolescents exhibited lower CREB activity in the vStr than LLA adolescents and this difference was attenuated by repeated exposure to high, but not low doses of nicotine. Thus, inherent differences in the reactivity to novel stimulation during the adolescent period appear to predict sensitivity to the behavioral and cellular effects of nicotine and may underlie differences in progression to addiction.
Laboratory of Neuropsychopharmacology, Department of Psychiatry and Neurosciences, University of South Florida College of Medicine, 3515 East Fletcher Avenue, Tampa, FL 33613, United States. rphilpot@health.usf.edu
Rex M
RM
Philpot
Melanie E
ME
Engberg
Lynn
L
Wecker
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001479:Basal Ganglia / Q000187:drug effects* / Q000378:metabolism*; D050882:CREB-Binding Protein / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D018722:Nicotinic Agonists; D009538:Nicotine; D050882:CREB-Binding Protein; C494365:Crebbp protein, rat