title: Exploring behavioral and molecular mechanisms of nicotine reward in adolescent mice.
abstract: Tobacco smoking during adolescence has become a prominent preventable health problem faced in the United States. Addictive properties of smoking are thought to have a pronounced effect at a young age, thereby increasing vulnerability to a life-long addiction and decreasing the likelihood of smoking cessation during adulthood. Learning and memory involvement in nicotine reward was assessed in early adolescent (PND 28-34) and adult (PND 70+) male ICR mice by conducting conditioning sessions of nicotine (0.5mg/kg) acquisition at varying time-spans, and evaluating extinction and reinstatement of nicotine preference using Conditioned Place Preference. Acquisition studies resulted in a significant preference for nicotine after 3 days of conditioning for both age groups, but not after only 1 or 2 conditioning days. In the extinction study, adolescent mice exhibited preference for nicotine 72 h after the last conditioning session, whereas preference for nicotine was extinct in adult mice by 72 h. Reinstatement studies showed adolescent mice, but not adult mice, recovering nicotine preference after a priming injection of 0.1mg/kg nicotine on day 9 after the mice underwent extinction. No significant differences were found when nAChRs were quantified in both early adolescent and adult mice using binding techniques including cytisine sensitive, α-conotoxin-MII sensitive, and α-bungarotoxin sensitive nAChRs. Levels of striatal dopamine release were measured in both age groups using a dopamine release assay over a range of nicotine doses, which also resulted in no significant differences. More sensitive assays may facilitate in understanding the mechanisms of nicotine reward in adolescent mice.
authors.affiliation: Department of Pharmacology and Toxicology, Medical Campus, Virginia Commonwealth University, Richmond, VA 23298-0613, United States.
authors.forename: Dena
authors.initials: D
authors.lastname: Kota
authors.forename: Sarah
authors.initials: S
authors.lastname: Sanjakdar
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Marks
authors.forename: Omar
authors.initials: O
authors.lastname: Khabour
authors.forename: Karem
authors.initials: K
authors.lastname: Alzoubi
authors.forename: M Imad
authors.initials: MI
authors.lastname: Damaj
mesh_terms: D000375:Aging / Q000523:psychology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003216:Conditioning, Operant / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D005106:Exploratory Behavior / Q000187:drug effects*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009538:Nicotine / Q000009:adverse effects*; D011485:Protein Binding; D011978:Receptors, Nicotinic / Q000378:metabolism; D012201:Reward
chemical_list: D011978:Receptors, Nicotinic; D009538:Nicotine; D004298:Dopamine