EXAMINING THE IMPACT OF ADOLESCENT NICOTINE EXPOSURE ON BEHAVIORAL LATER IN LIFE

1. EXAMINING THE IMPACT OF ADOLESCENT NICOTINE EXPOSURE ON BEHAVIORAL LATER IN LIFE Mai Alajaji M.S. and M. Imad Damaj Ph.D.Department of Pharmacology & Toxicology, Virginia Commonwealth University, Richmond, VA 23298 USA 28 34 46 59 70+ PND Results Introduction Results • Nicotine is one of the first and most commonly abused drugs in adolescence. Over 4500 adolescents start smoking every day in the United States (Chassin et al. 1990). • The commencement of smoking at a young age is thought to increase addiction, decrease the probability of successful cessation, and correlates with a higher number of cigarettes smoked per day (Colby et al. 2000; Kandel and Chen 2000;Taoli and Wynder 1991). • This suggests that adolescence is a critical period for the initiation and maintenance of tobacco use. • Smoking among adolescents is a strong predictor of future drug abuse and dependence in adulthood. • Recent data from our lab showed that early adolescent nicotine exposure causes increased rewarding effects of nicotine in adulthood (Kota et al. 2009). The Enhancement of Cocaine Reward by Nicotine is Strain-Dependent ** $ * * * Hypothesis Adult DBA ,C57B6/J and ICR mice were exposed to nicotine 0.5 mg/kg, S.C., bid., for 7-days)or saline during adolescence PND28.*p<.05 fromrespective sal-sal; **p<.05 fromrespective C57 sal-coc (10) $p<.05 fromrespective ICR Sal-coc (10) We hypothesize that nicotine exposure during adolescence causes long lasting neurobiological alterations that increase the susceptibility to cocaine reward in adulthood. Furthermore, it will activate a neurobiological mechanism that is shared by many drugs of abuse, which will increase susceptibility to their rewarding effects. Conclusion /Future Directions Materials & Methods • Conclusion: • -EARLY, but not late adolescence is a critical period of development during which drug exposure can cause long-lasting alterations in behavior specifically reward. • -Adolescent nicotine exposure is able to enhance the behavioral effects(acute locomotors and rewards) of cocaine in adulthood. • -The enhancement of cocaine rewards by nicotine in adulthood is dose- ,duration- ,strain- and age-dependent. • -The enhancement of cocaine reward by nicotine isa4b2 nAChRs –mediated. • - Similarly, exposure to nicotine in early adolescence has persistent effects on amphetamine and morphine dependence in adulthood. • -Taken together, our data suggests that adolescent nicotine exposure may cause dopaminergic alterations which lead to enhanced vulnerability to drug dependence later in life. Preventing adolescent experimentation with nicotine is extremely important as it can rapidly cause persistent changes in drug-induced behavioral responses. • Future Direction: • Conditioned-place-preference and acute locomotors paradigms were used to examine changes in cocaine sensitivity in adulthood. Testing was performed on adult ICR mice that were exposed to nicotine (0.1 or 0.5 mg/kg, S.C., bid., for 7-days) or saline during adolescence (postnatal days 28 or 46) or adult (postnatal day 70). • Acute Locomotors Activity • DRC: 5 and 20 mg/kg i.p. cocaine • Reward: Cocaine-induced CPP • Early and late adolescent exposure • Cocaine conditioning dose :10 mg/kg i.p. • Morphine conditioning dose :5 mg/kg s.c • D- amphetamine conditioning dose :0.2mg/kg s.c Nicotine  Accumulating delta FosB enhance cocaine CPP References or Bibliography measure ΔFosB expression in adolescent mice compared to adults using western blotting for ΔFosB Alteration of Synaptic plasticity enhance cocaine effects. Incubation time Figure (A-D),Cocaine-induced conditioned place preference in adulthood after previous nicotine exposure. Results are expressed as mean preference scores +/- SEMs (n=8/group). *P<0.05 (significant difference from sal-coc(10). Acute exposure=a single day of injections; Repeated exposure=injections every day for 7 days(2x/day, approximately 6 hrs. a part; s.c. ). Figure (E & F), Amphetamine and Morphine induced conditioned place preference in adulthood after previous nicotine exposure. $P<0.05 (significant difference from sal-amp(0.2). #P<0.05 (significant difference from sal-mor(5). Figure (G),The onset of cocaine enhancement *P<0.05 (significant difference from sal-PND50. #P<0.05 (significant difference from sal-PND70 Figure (H),Cocaine-induced hyperactivity following nicotine exposure in Adulthood .Mice were pretreated with saline or nicotine during early adolescence repeatedly(7 days) and were tested for cocaine hyperactivity in adulthood. n=6/group .**P<0.05 (significant difference from sal-coc(20). Chassin L, Presson CC, Sherman SJ, Edwards DA (1990) The natural history of cigarette smoking: predicting young-adult smoking outcomes from adolescent smoking patterns. Health Psychol. 1990;9(6):701-16. Colby SM, Tiffany ST, Shiffman S, Niaura RS (2000) Are adolescent smokers dependent on nicotine? A review of the evidence. Drug Alcohol Depend 59 Suppl 1:S83-95 Kandel DB, Chen K (2000) Extent of smoking and nicotine dependence in the United States: 1991-1993. Nicotine Tob Res 2(3):263-74 Taoli E and Wydner EL (1991) Effect of the age at which smoking begins on frequency in adulthood. New Engl. J. Med. 325:968-969. Acknowledgements Figure (I), The effects of early adolescent DHEβ-nicotine exposure (7-day) on cocaine-induced CPP in adulthood. Mice were pretreated with saline ,nicotine , DHEβ (2mg/kg) or DHEβ and nicotine during early adolescence (n=8/group) # p<.05 from sal-coc(10). • Virginia Foundation For Healthy Youth for their funding. • Dena Kota and Cindy Evans for their technical assistance. Contact information