Context dependent effects of heroin self administration on nucleus accumbens synaptic plasticity

We have previously reported the setting of drug self-administration has a powerful influence on drug intake(Caprioli et al. 2008). Rats that lived in the self-administration (SA) chamber (ResidentRats) tended to self-administer more heroin than rats that were exposed to the SA chamber only during testing (NonResidentRats living in a distinct home cage). Also the neurobiological effects of heroin are a function of setting. In situ hybridization and immunohistochemistry experiments have shown that the effects of heroin on the expression of FosmRNA and Fos in the reward regions of the brain are very different in Resident vs. NonResidentRats (Paolone et al. 2007; Celentano et al. 2009). Fos is a transcription factor that is thought to be implicated in the early stages of drug-induced neuroplasticity. Thus, we hypothesized that the setting may influence heroin-induced long term plasticity.In the present study, we used ex vivo electrophysiological recordings to investigate the effects of heroin SA on long term cortico-accumbens synaptic plasticity as a function of setting. Both Resident and NonResident rats were trained to self-administer heroin (25μg/kg/infusion) for 10sessions (3h each).After 14 days of abstinence from heroin the rats were killed and their brains excised to obtain parasagittal slices for field recordings. We found that after tetanic stimulation, LTP was greater in NonResidentRats (fEPSP amplitude about 160% of baseline) than in ResidentRats (140% of baseline). This suggests that cortico-accumbens (presumably inhibitory) inputs are reduced when the rats self-administer heroin in their home environment relative to a non-home setting and may explain why ResidentRats tend self-administer more heroin than NonResidentRats