Several reports have indicated that, under different experimental conditions, the administration of
histamine H(3)-receptor antagonists exerts procognitive effects by activating central histaminergic transmission. In the present study the action of
thioperamide, a H(3)-receptor blocker, is investigated on consolidation and recall mechanisms of the rat place recognition memory. The animals have been tested on a two-trial delayed comparison paradigm in a Y-maze.
Thioperamide enhances the memory retention when administered intraperitoneally (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 rat performance when injected 45 min prior to the testing trial. The post-acquisition 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 memory. In addition,
thioperamide reverses the
amnesia induced by the post-acquisition treatment with 0.02 mg/kg i.p. of
scopolamine (SCOP). The procognitive effect of
thioperamide is not modified by the contemporary administration of
pyrilamine, an
histamine H(1)-receptor antagonist. On the contrary, the blockade of H(2)-receptors by
zolantidine 10 mg/kg reverses both the effect of
thioperamide alone and the
drug action on the
scopolamine-induced
memory deficit. The results indicate that the neuronal
histamine released in consequence of the post-acquisition
thioperamide treatment improves place recognition memory through the activation of postsynaptic H(2)-receptors.