Effects of histamine H3 receptor agonists and antagonists on cognitive performance and scopolamine-induced amnesia

In previous research we found that pre-training administration of histamine H-3 receptor agonists such as (R)-alpha-methylhistamine and imetit impaired rat performance in object recognition and a passive avoidance response at the same doses at which they inhibited the release of cortical acetylcholine in vivo. Conversely, in the present study we report that the post-training administration of (R)-alpha-methylhistamine and imetit failed to affect rat performance in object recognition and a passive avoidance response, suggesting that H-3 receptor influences the acquisition and not the recall processes. We also investigated the effects of two H-3 receptor antagonists, thioperamide and clobenpropit, in the same behavioral tasks. Pre-training administration of thioperamide and clobenpropit failed to exhibit any precognitive effects in normal animals but prevented scopolamine-induced amnesia. However, also post-training administration of thioperamide prevented scopolamine-induced amnesia. Hence, the ameliorating effects of scopolamine-induced amnesia by H-3 receptor antagonism are not only mediated by relieving the inhibitory action of cortical H-3 receptors, but other mechanisms are also involved. Nevertheless, H-3 receptor antagonists may have implications for the treatment of degenerative disorders associated with impaired cholinergic function. (C) 1999 Elsevier Science B.V. All rights reserved.