Involvement of D₂ dopamine receptors in the opposing effects of two CCK-B agonists in a spatial recognition memory task: role of the anterior nucleus accumbens

Abstract.

Rationale: A previous study in the rat has shown that systemic injection of two CCK-B agonists, BC264 and BC197, induced opposing effects on the retrieval phase of a spatial recognition memory task. Objective: The present study was designed to investigate the mechanisms underlying these effects at the level of the dopaminergic system. Methods: Rats were injected IPly with BC264 (0.3 µg/kg) or BC197 (30 µg/kg) and with D₁ or D₂ agonists and antagonists. The cognitive performances of rat were analysed on the retrieval phase of a spatial recognition memory task. The extracellular levels of dopamine were quantified in the anterior nucleus accumbens after injection of BC197 (3, 30 and 300 µg/kg IP), using the microdialysis technique on freely moving rats. Local injection of the D₂ antagonist, sulpiride (2.5 ng/µl) was performed in the anterior nucleus accumbens and the cognitive performances analysed following systemic injection of BC264 (0.3 µg/kg). Results: The improvement and the impairment of performance induced respectively by BC264 and BC197 were suppressed by peripheral administration of sulpiride, showing that these opposing effects were both mediated by the stimulation of D₂-like receptors. However, different dopaminergic pathways seem to be involved in the effects of the two CCK-B agonists. Indeed, systemic administration of BC197 did not induce the increase of extracellular dopamine levels observed with BC264. Furthermore, local injection of sulpiride, in the anterior nucleus accumbens, completely suppressed the cognitive enhancing effect of BC264. Conclusion: These findings suggest that the D₂-mediated deficit in the performance induced by BC197 involves brain structures other than the anterior nucleus accumbens. They also demonstrate a critical role of dopaminergic transmission within the anterior nucleus accumbens in the improving effect induced by BC264 in a spatial memory task.