Cholecystokinin-octapeptide restored morphine-induced hippocampal long-term potentiation impairment in rats

Cholecystokinin-octapeptide (CCK-8), which is a typical brain-gut peptide, exerts a wide range of biological activities on the central nervous system. We have previously reported that CCK-8 significantly alleviated morphine-induced amnesia and reversed spine density decreases in the CA1 region of the hippocampus in morphine-treated animals. Here, we investigated the effects of CCK-8 on long-term potentiation (LTP) in the lateral perforant path (LPP)-granule cell synapse of rat dentate gyrus (DG) in acute saline or morphine-treated rats. Population spikes (PS), which were evoked by stimulation of the LPP, were recorded in the DG region. Acute morphine (30 mg/kg, s.c.) treatment significantly attenuated hippocampal LTP and CCK-8 (1 μg, i.c.v.) restored the amplitude of PS that was attenuated by morphine injection. Furthermore, microinjection of CCK-8 (0.1 and 1 μg, i.c.v.) also significantly augmented hippocampal LTP in saline-treated (1 ml/kg, s.c.) rats. Pre-treatment of the CCK2 receptor antagonist L-365,260 (10 μg, i.c.v) reversed the effects of CCK-8, but the CCK1 receptor antagonist L-364,718 (10 μg, i.c.v) did not. The present results demonstrate that CCK-8 attenuates the effect of morphine on hippocampal LTP through CCK2 receptors and suggest an ameliorative function of CCK-8 on morphine-induced memory impairment.