Dose- and time-dependent, context-induced elevation of dopamine and its metabolites in the nucleus accumbens of morphine-induced CPP rats

The dopamine (DA) projections from the ventral tegmental area to the nucleus accumbens (NAc) are the key component of the brain reward circuitry. The encoded information by DA in reward-related memory within this circuit during opiate reinforcement requires further clarification. The present study was designed to explore the correlations between morphine dose, retention of morphine-induced conditioned place preference (CPP), morphine-induced changes in levels of DA and its metabolites in the NAc in expression and retention of CPP in Sprague-Dawley male rats. A dose-effect curve for morphine-induced CPP (0.01-10 mg/kg, i.p.) was obtained using 4-day conditioning sessions followed by a CPP test; the retention of morphine CPP was measured with CPP tests after the development of CPP. We found a dose-dependent effect of morphine (from 0.01 to 10.0 mg/kg, i.p.) on both the magnitude and the retention of CPP. During the retention of morphine-induced CPP, a morphine-dose- and time-dependent elevation of DA and its metabolites was observed in the NAc. These changes were absent if the same dose of morphine was injected outside of the conditioning environment (i.e., in the home cage). These results suggest that that the long-lasting elevation of DA and its metabolites in the NAc is attributable mainly to drug-associated context, rather than the residual effect of morphine.