Involvement of D-2 dopamine receptors in the opposing effects of two CCK-Bagonists in a spatial recognition memory task: role of the anterior nucleus accumbens

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 retri eval phase of a spatial recognition memory task. Objective: The present stu dy was designed to investigate the mechanisms underlying these effects at t he level of the dopaminergic system. Methods: Rats were injected IPly with BC264 (0.3 mug/kg) or BC197 (30 mug/kg) and with D-1 or D-2 agonists and an tagonists. The cognitive performances of rat were analysed on the retrieval phase of a spatial recognition memory task. The extracellular levels of do pamine were quantified in the anterior nucleus accumbens after injection of BC197 (3, 30 and 300 mug/kg IP), using the microdialysis technique on free ly moving rats. Local injection of the D-2 antagonist, sulpiride (2.5 ng/mu l) was performed in the anterior nucleus accumbens and the cognitive perfor mances analysed following systemic injection of BC264 (0.3 mug/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 D-2-like receptors. However, different dopaminergic pathways seem to be involved in the effects of the two CCK-B agonists. Indeed, systemic adminis tration of BC197 did not induce the increase of extracellular dopamine leve ls observed with BC264. Furthermore, local injection of sulpiride, in the a nterior nucleus accumbens, completely suppressed the cognitive enhancing ef fect of BC264. Conclusion: These findings suggest that the D-2-mediated def icit in the performance induced by BC197 involves brain structures other th an the anterior nucleus accumbens. They also demonstrate a critical role of dopaminergic transmission within the anterior nucleus accumbens in the imp roving effect induced by BC264 in a spatial memory task.