Drug addiction is one of the most costly and devastating health problems in the United States. Adolescents are particularly susceptible to drugs of abuse, in part because they are motivated to take risks and they seek the social approval among their peers. While the neurobiology underlying the affiliative social behaviors of adults has been extensively studied over last few years, there neurobiology of adolescent social behaviors is not well understood and may represent distinct genetic influences. In support of this concept, we find that social approach behaviors among two strains of juvenile mice (BALB/c and C57BL/6) exhibit strain- dependent differences that are not influenced by gender. As these mice mature, strain-specific differences are displaced by the emergence of gender-specific differences in social behavior, suggesting distinct underlying genetics and neurobiology of adolescent and adult social behavior. The central hypothesis of this proposal is that drugs of abuse may co-opt social reward pathways of the adolescent phenotype. Opioids can interfere with adolescent social interactions and we find higher sensitivity towards opioids in the juvenile mouse strain that shows greater pro-social tendencies. We propose to examine (a) how natural rewards, such as access to social interactions and highly palatable foods, affect reward pathways in the adolescent mouse brain, (b) how the social environment affects the neural and behavioral response to morphine, (c) how morphine influences social approach and arousal and (d) the extent to which social reward is influenced by the concurrent manipulation of opioid receptors. With this foundation for understanding the adolescent mouse brain and behavior, we can envision a long-term research program that employs genetic and genomic strategies to elucidate the interplay between drugs of abuse and social approach during this unique period of development.
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