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 (0.5 mg/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 0.1 mg/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.

Reward Anticipation Is Encoded Differently by Adolescent Ventral Tegmental Area Neurons

“…Accordingly, adolescents demonstrate greater reinstatement of conditioned place preference for drugs of abuse [43, 44]. VTA dopamine neurons, through their projections to ventral striatum and prefrontal cortex, play a critical role in value learning, attention and working memory [45, 46].…”

Reward-centricity and attenuated aversions: An adolescent phenotype emerging from studies in laboratory animals

“…Converging evidence from a number of sources has led to the suggestion that elevations in D1R expression in frontal cortex may impart a vulnerability for drug-associated cues, while also contributing to adolescent-motivated behaviors (Brenhouse and Andersen, 2008; Brenhouse et al, 2008; Kota et al, 2011; Leslie et al, 2004). One recent approach providing data consistent with the suggestion of an involvement of D1Rs in expression of adolescent-typical behaviors comes from work assessing consequences of lentivirus-induced overexpression of D1Rs in the prelimbic PFC of adult rats.…”

Nicotine, adolescence, and stress: A review of how stress can modulate the negative consequences of adolescent nicotine abuse

“…No drugs are administered on testing days and time spent in the prior drug-paired side indicates higher rewarding properties of the drug (Tzschentke, 1998). Kota et al (2011) examined differences between adolescent (P28–36) and adult (P70) ICR mice using three drug pairings at 5 different doses. It was found that adolescent mice conditioned with nicotine acquired CPP at 0.05mg/kg, 0.1mg/kg, and 0.5 mg/kg compared to saline controls.…”