Social environment modulates morphine sensitivity: A partial role of vasopressin V1b receptor

Abstract

Social factors influence drug abuse in adolescents; this is partially attributed to peer pressure in humans. Similarly, using rodent models, some research suggests that social housing condition can influence rodents' drug taking behavior. Despite this, few studies have examined the role that intoxicated peers have on drug-naive cage-mates. This dissertation examined how social environment affects opioid sensitivity and hormone production. This was accomplished by comparing the opioid sensitivity of mice housed in mixed cages (some animals received opioids and some were drug-naive) to cages where all the mice were treated with the same drug (all saline or all morphine). These studies identified an adolescent-specific vulnerability to social environment-induced alteration of morphine sensitivity. Interaction with drug-intoxicated cage-mates enhanced locomotor sensitivity in previously drug-naive males and altered their production of testosterone. Conversely, interaction of morphine experienced mice with drug-naive cage-mates afforded protection from the rewarding properties of morphine. In other words, morphine-treated mice housed with drug-naive cage-mates demonstrated attenuated reward compared to morphine-treated mice housed with other morphine-treated mice. In addition, part of the neurobiological basis of the social-environment effect was identified. Antagonism of V1b receptors decreased morphine reward in morphine-treated mice housed only with other morphine-treated mice. These results suggest a role of vasopressin in the peer influence on drug sensitivity observed in adolescents. This body of work further elucidates the role of peer influence on opioid sensitivity. Future studies should further reveal the role of healthy peer relationships and should aid in combating drug abuse in this at-risk demographic.