Social Deprivation Enhances VTA Synaptic Plasticity and Drug-Induced Contextual Learning

Drug addiction is driven, in part, by powerful drug-related memories. Deficits in social life, particularly during adolescence, increase addiction vulnerability. Social isolation in rodents has been used extensively to model the effects of deficient social experience, yet its impact on learning and memory processes underlying addiction remains elusive. Here, we show that social isolation of rats during a critical period of adolescence (postnatal days 21-42) enhances long-term potentiation of NMDA receptor (NMDAR)-mediated glutamatergic transmission in the ventral tegmental area (VTA). This enhancement, which is caused by an increase in metabotropic glutamate receptor-dependent Ca2+ signaling, cannot be reversed by subsequent resocialization. Notably, memories of amphetamine- and ethanol-paired contextual stimuli are acquired faster and, once acquired, amphetamine-associated contextual memory is more resistant to extinction in socially isolated rats. We propose that NMDAR plasticity in the VTA may represent a neural substrate by which early life deficits in social experience increase addiction vulnerability.