The Role of Social Environment on Morphine Response in Adolescent Mice

Drug abuse is strongly influenced by socio-environmental factors. Also, social environment is one of the most important predictors for adolescent drug use. In this dissertation, I examined how social housing conditions affect morphine reward, dependence, and antinociception. I also explored possible mechanisms that may underlie these responses. Mice were group-housed in one of two conditions referred to as ‘only’ and ‘mixed’. In the only condition, all mice in the cage receive the same treatment and are physically and visually separated from mice that receive different treatments (i.e., saline only and morphine only). Mice in the mixed condition were housed together with mice that received a different treatment- (i.e., morphine cage-mate mice are housed with drug naïve mice and saline cage-mate mice are housed with morphine-treated mice). Being housed with drug-naive mice conferred a protective effect for the rewarding properties of morphine, as well as the occurrence of withdrawal symptoms. Similarly, while it did not prevent the development of tolerance to morphine analgesia, it did reduce the persistence of this tolerance. Moreover, it provided protection from morphine-induced hyperalgesia. Additionally, some of the neurobiological mechanisms underlying this protection were identified. Inhibiting the sensation of social grooming in morphine cage-mates blocked the protective effect of being housed with drug-naïve animals. Additionally, increased expression of vasopressin mRNA was observed in the striatum of morphine only animals, while being housed with drug-naïve mice protected against this effect. In line with this finding, antagonizing V1b receptors blocked the development of morphine reward in morphine only animals. Lastly, I identified various genes with increased expression levels in striatum of morphine only animals, but not morphine cage-mates. This makes them potential targets for future studies aiming to reveal the underlying molecular mechanisms involved in the protective effects of being housed with drug-naïve animals. These studies further support the notion that social conditions alter the propensity for developing opioid addiction, and can be used in the development of more efficacious behavioral and pharmacological treatments for adolescent opioid addicts