Morphine-conditioned single-trial place preference: role of nucleus accumbens shell dopamine receptors in acquisition, but not expression

Rationale: A large body of evidence indicates an involvement of the mesolimbic dopamine (DA) pathway innervating the ventral striatum in the motivational effects of drug abuse. Objective: The goal of the study is to clarify the role of DA D-1 and D-2 receptors of the rat nucleus accumbens (NAc) shell and core in the motivational effects of morphine as studied by conditioned place preference (CPP). Methods: The effect of the intracerebral infusion of DA antagonists specific for DA D-1 (SCH 39166) and D-2 receptors (L-sulpiride) was studied in a single-trial place conditioning paradigm with fixed assignment of the drug to the unpreferred compartment. Results: Morphine induced significant CPP at all the doses tested (0.5, 1.0, and 2.0 mg/kg, subcutaneously). A dose of 1.0 mg/kg was selected for further studies. Intra-NAc shell infusion of SCH 39166 and L-sulpiride at doses of 25 and 50 ng/1 mu l per side impaired the acquisition of CPP by morphine. No effect was observed at 12.5 ng/1 mu l per side. Intra-NAc core infusion of SCH 39166 (12.5, 25, and 50 ng/1 mu l per side) did not affect the acquisition of morphine-induced CPP, while L-sulpiride (12.5, 25, and 50 ng/1 mu l per side) impaired CPP acquisition only at the dose of 50 ng/1 mu l per side. No effect on morphine-induced CPP was observed when the DA antagonists were infused into the NAc shell or core 10 min before the test session. Conclusion: These results indicate that DA D-1 and D-2 receptors in the NAc shell are involved in the acquisition of morphine-induced CPP.