There is a significant need for better prevention and intervention strategies for smoking and nicotine dependence. Progress in this area relies upon understanding the biological and behavioral mechanisms involved in various stages of addiction, including initiation. Initial drug experiences typically take place in adolescence and nearly always in the presence of peers who provide social reinforcement for the behavior, yet the neural mechanisms involved in social influences on drug initiation are poorly understood. Animal models demonstrate that in adolescents, social interactions enhance the rewarding effects of commonly abused drugs, including nicotine. Nicotine and other drugs of abuse elevate corticosteroids (CORT) via activation of the hypothalamic-pituitary-adrenal (HPA) axis, which is the body's response to stressors. Social buffering is a well- known phenomenon in the stress literature in which the presence of a conspecific promotes better recovery from stressful stimuli by alleviating negative physiological and behavioral responses to stress. Stress and reward both activate mesocorticolimbic pathways in the brain, which are involved in processing emotional stimuli and translating it into motivated behavior. These pathways and the HPA axis are reciprocally regulated. Recently, our lab has found that nicotine-induced CORT elevation is attenuated by a social context. Therefore, we hypothesize that social buffering during initial the experience with nicotine renders adolescents more resilient to initial anxiogenic effects of the drug by inhibiting the HPA axis and modulating mesocorticolimbic processing, resulting in increased reward salience. To test our hypothesis, we will investigate nicotine-induced HPA-axis activation and anxiety-related behavior in an open field in rats tested alone versus in familiar pairs. We will then examine whether this initial drug experience renders the next drug experience more rewarding in rats that were with another rat following their first injection relatie to those that were alone using the conditioned place preference (CPP) model. Finally, we will measure activation of brain regions implicated in processing stressful stimuli using expression of the immediate early gene protein product, Fos as a marker. Examination of neural activation will be focused primarily on identifying excitatory and inhibitory cells within the bed nucleus of stria terminals (BNST), a region of the brain highly implicated in anxiety processing. We predict that rats that receive social interaction in combination with nicotine will demonstrate less anxiety-lik behaviors in the open field test, show an attenuated CORT response, display enhanced drug-CPP, and exhibit less activation of stress and anxiety-related brain structures. The findings will aid in elucidating the mechanisms involved in social and nicotine reward interactions during initial drug exposure. This information is significant and may inform the development of new prevention and intervention strategies for drug abuse because the degree to which one finds the first drug experience rewarding is thought to predict the propensity for drug abuse and dependence.

Public Health Relevance

Initiation of smoking typically occurs during adolescents or young adulthood with peers providing social reinforcement for the behavior. We aim to investigate social influences on initial drug experiences and the neural mechanisms underlying these effects in adolescent rats. This research is important because the degree to which one finds initial drug experiences rewarding predicts the likelihood of dependence, yet preclinical models aimed at the neural mechanisms of initiation have largely overlooked the contribution of social context to initial drug reward.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Predoctoral Individual National Research Service Award (F31)
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Special Emphasis Panel (ZRG1-F02A-J (20))
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Babecki, Beth
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Arizona State University-Tempe Campus
Other Basic Sciences
Schools of Arts and Sciences
United States
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Peartree, Natalie A; Hatch, Kayla N; Goenaga, Julianna G et al. (2017) Social context has differential effects on acquisition of nicotine self-administration in male and female rats. Psychopharmacology (Berl) 234:1815-1828
Bastle, Ryan M; Peartree, Natalie A; Goenaga, Julianna et al. (2016) Immediate early gene expression reveals interactions between social and nicotine rewards on brain activity in adolescent male rats. Behav Brain Res 313:244-254
Pentkowski, Nathan S; Harder, Bryan G; Brunwasser, Samuel J et al. (2014) Pharmacological evidence for an abstinence-induced switch in 5-HT1B receptor modulation of cocaine self-administration and cocaine-seeking behavior. ACS Chem Neurosci 5:168-76