Evidence for heroin-induced social isolation in the rat

A critical feature of opioid use disorder (OUD) is the progressive loss of interest and decreased investment in social relationships. State of the art OUD preclinical choice models do not capture this aspect. Counterintuitively, when rats face a choice between heroin infusion and social interaction, rats strongly prefer social rewards over heroin. Here, we investigated the procedural reasons that might be responsible for this key limitation. Typically, during extended periods of heroin self-administration rats learn to self-administer ‘loading’ doses of drug, featured by a high rate of infusions. This pattern closely resembles the behavior of heroin users: taking large doses of heroin through the fastest route of administration to experience a euphoric ‘rush’. However, in the choice procedure, rats are allowed to choose between one unit-dose of heroin or social interaction. In a series of experiments, by combining behavioral and pharmacokinetics assessments, we provide evidence that this suboptimal dosing strategy (experimenter imposed) during the choice procedure prevents the emergence of social deficits (voluntary social isolation in favor to heroin taking) evident in a subgroup of rats.