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 D1 and D2 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 D1 (SCH 39166) and D2 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 microl per side impaired the acquisition of CPP by morphine. No effect was observed at 12.5 ng/1 microl per side. Intra-NAc core infusion of SCH 39166 (12.5, 25, and 50 ng/1 microl per side) did not affect the acquisition of morphine-induced CPP, while L-sulpiride (12.5, 25, and 50 ng/1 microl per side) impaired CPP acquisition only at the dose of 50 ng/1 microl 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 D1 and D2 receptors in the NAc shell are involved in the acquisition of morphine-induced CPP.
Morphine-conditioned single-trial place preference: role of nucleus accumbens shell dopamine receptors in acquisition, but not expression
FENU, SANDRO;SPINA, LILIANA;DI CHIARA, GAETANO
2006-01-01
Abstract
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 D1 and D2 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 D1 (SCH 39166) and D2 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 microl per side impaired the acquisition of CPP by morphine. No effect was observed at 12.5 ng/1 microl per side. Intra-NAc core infusion of SCH 39166 (12.5, 25, and 50 ng/1 microl per side) did not affect the acquisition of morphine-induced CPP, while L-sulpiride (12.5, 25, and 50 ng/1 microl per side) impaired CPP acquisition only at the dose of 50 ng/1 microl 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 D1 and D2 receptors in the NAc shell are involved in the acquisition of morphine-induced CPP.
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