Peer presence and familiarity as key factors to reduce cocaine intake: an effect mediated by the Subthalamic Nucleus

Abstract

Stimulant use, including cocaine, often occurs in a social context whose influence is important to understand to decrease intake and reduce associated harms. Given the regulatory role of the subthalamic nucleus (STN) on cocaine intake and emotions, we investigate its role on such influence of social context on cocaine intake. We explored the influence of peer presence and familiarity on the frequency of self-administered cocaine and its neurobiological basis. We first compared cocaine intake in various conditions (alone or with peers with different characteristics: observing or self-administering, familiar or not, cocaine-naive or not, dominant or subordinate) in rats (n=90). The risk of drug consumption was reduced when a peer was present, observing or self-administering as well, and further diminished when the peer was unfamiliar (vs familiar). The presence of a cocaine-naive peer further decreased cocaine consumption. The presence of a non-familiar and drug-naive peer represents thus key conditions to diminish cocaine intake. We tested the effects of STN lesions in these various conditions and also conducted social experiments to validate the role of STN in social cognition. The STN lesion by itself reduced cocaine intake to the level reached in presence of a stranger naive peer and affected social cognition, positioning the STN as one neurobiological substrate of social influence on drug intake. Finally, with a translational research approach, we compared the drug intake in these conditions in human drug users (n=77). This human study confirmed the beneficial effect of social presence, especially of strangers. Our results indirectly support the use of social interventions and harm reduction strategies, in particular supervised consumption rooms for stimulant users.