A study on the mechanism of mnemonic effect of vasopressin and vasopressin fragment analog

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In order to study the action mechanism of vasopressin or its fragment analog, we examined a relationship between the mnemonic effect of these peptides and glutamatergic receptor in the behavioral study. The administration of a NMDA receptor antagonist, or a metabotropic glutamate receptor antagonist, inhibited the performance in memory task. The mnemonic effect of the peptides was decreased by the co-administration with these antagonists. These results suggested that the mnemonic effect of the peptides attributed to the glutamatergic neuron activity via NMDA and/or group I metabotropic glutamate receptor.A relationship between retrograde neurotransmitter and action mechanism of VPMF or NC was also examined. Additionally, we investigated the influence of cyclooxygenase (COX) inhibition on mnemonic effect induced by the peptides, and some COX inhibitors were administrated immediately after the training in the water maze. A non-specific COX and a specific COX-2 inhibitors but not COX-1 in … More hibitor prolonged the latency in the water maze. The real time PCR showed that the administration of the COX-2 inhibitor decreased an appearance of COX-2 mRNA but not that of COX-1 in the brain, and the decrease of COX-2 mRNA was caused within 2 h after the administration of COX-2 inhibitor. These results suggested that endogenous COX-2 activation is needed to form the memory. The mnemonic effect of the peptides was decreased by the co-administration with the COX-2 inhibitor but not COX-1 inhibitor. These observations, together with our previous findings, suggest that the V1A receptors of the peptides are coupling with Gq/11 protein ; therefore, the activation of the V1A receptors induces activation of phospholipase C, protein kinase C, phospholipase A2. Consequently, these enzyme activations could cause the activation of endogenous COX-2, and the products (prostaglandin E2) may induce further activation of signal transduction of the enzymes, since prostaglandin E2 receptor is also coupled with Gq/11 protein. Less