Histamine H-3-receptor antagonism improves memory retention and reverses the cognitive deficit induced by scopolamine in a two-trial place recognition task

Several reports have indicated that, under different experimental condition s, the administration of histamine H-3-receptor antagonists exerts procogni tive effects by activating central histaminergic transmission. In the prese nt study the action of thioperamide, a H-3-receptor blocker, is investigate d on consolidation and recall mechanisms of the rat place recognition memor y. The animals have been tested on a two-trial delayed comparison paradigm in a Y-maze. Thioperamide enhances the memory retention when administered i ntraperitoneally (i.p.) post-acquisition (0.7 and 5.0 mg/kg are ineffective , whereas the dose of 2.0 mg/kg improves memory) but does not affect the ra t performance when injected 45 min prior to the testing trial. The post-acq uisition effect of thioperamide is time-dependent since the administration of the drug 30 min after the end of the training trial has no effect on mem ory. In addition, thioperamide reverses the amnesia induced by the post-acq uisition treatment with 0.02 mg/kg i.p. of scopolamine (SCOP). The procogni tive effect of thioperamide is not modified by the contemporary administrat ion of pyrilamine, an histamine H-1-receptor antagonist. On the contrary, t he blockade of H-2-receptors by zolantidine 10 mg/kg reverses both the effe ct of thioperamide alone and the drug action on the scopolamine-induced mem ory deficit. The results indicate that the neuronal histamine released in c onsequence of the post-acquisition thioperamide treatment improves place re cognition memory through the activation of postsynaptic H-2-receptors. (C) 2001 Elsevier Science B.V. All rights reserved.