CCK-A AND CCK-B SELECTIVE RECEPTOR AGONISTS AND ANTAGONISTS MODULATE OLFACTORY RECOGNITION IN MALE-RATS

Modulation of learning and memory is one of the physiological roles th at the neuropeptide cholecystokinin (CCK-8) may play. We have used a b ehavioural model of olfactory recognition among rats to test this hypo thesis and to explore the relationship between CCK-A and CCK-B recepto rs and memory retention. Adult male rats form a transient memory of a juvenile congenere as indicated by a reduction in the duration of inve stigatory behaviour upon re-exposure 30 min after an initial exposure, but not when re-exposure is delayed until 120 min afterwards. In the present study, rats were treated after the first contact with various compounds; inhibition and facilitation of olfactory recognition were e valuated as the persistence in investigation 30 min and the decrease i n investigation 120 min after pharmacological manipulations, respectiv ely. Systemic injection of CCK-8, of a selective CCK-A agonist, or of non-peptide CCK-B antagonists (CI-988 and LY-262691) enhanced olfactor y recognition. In contrast, the CCK-B selective agonist BC 264 and the tetrapeptide CCK-4 both disrupted it. Taken together with previous ev idence of the detrimental effect of the nonpeptide CCK-A antagonist de vazepide on olfactory recognition, these results confirm and extend th e hypothesis that there is a balance between CCK-A-mediated facilitati ve effects and CCK-B-mediated inhibitory effects on memory retention.