Environmental novelty causes stress-like adaptations at nucleus accumbens synapses: implications for studying addiction-related plasticity.

Exposure to abused drugs and stressful experience, two factors that promote the development of addiction, also modify synaptic function in the mesolimbic dopamine system. Here, we show that exposure to a novel environment produces functional synaptic adaptations in the nucleus accumbens (NAc) that mirror the effect of conventional forms of stress. We find an enhancement of excitatory synaptic strength in the NAc shell one day after exposure to a novel environment for 60 min--an effect not observed in NAc core. This effect disappeared following repeated exposure to the same environment, but then reappeared if mice are returned to the same environment 10-14 days later. There were no interactions between the effects of environmental novelty and a single exposure to cocaine (15 mg/kg), with no effect of the latter on synaptic strength in NAc shell. These results have important implications for designing studies of NAc synapses in the context of behavioral analysis, and expand our understanding of how different forms of stress modify NAc synaptic function.