Histamine H₃-receptor blockade in the rat nucleus basalis magnocellularis improves place recognition memory

Abstract

Rationale: Several lines of evidence have indicated that the central histaminergic system might be involved in learning and memory Objectives: The aim of the present study was to ascertain the impact on memory processes of putative histaminergic–cholinergic interactions in the nucleus basalis magnocellularis (NBM) of the rat. Methods: The effects of thioperamide, a histamine H₃-receptor antagonist, were studied on the memory performance of rats in a two-trial, delayed, place-recognition task. The drug was injected into the NBM area 2 min prior to the first trial (1.5, 7.5, and 37.5 ng/0.5 µl; pre-acquisition treatment), within 30 s from the end of the first trial (0.3, 1.5, 7.5, and 37.5 ng/0.5 µl; post-acquisition treatment), or 2 min prior to the second trial (1.5, 7.5, and 37.5 ng/0.5 µl; pre-retrieval treatment). Results: Post-acquisition intra-NBM injections of 1.5 ng and 7.5 ng, but not of 0.3 ng and 37.5 ng thioperamide, significantly enhanced memory retention in treated rats. The histamine H₃-receptor blocker exerted pro-cognitive effects only when administered post-acquisition, since both pre-acquisition and pre-retrieval treatments were ineffective. The post-acquisition effect of the drug was time dependent and disappeared when the drug was injected 90 min after the end of the first trial. The U-shaped dose–response relationship and the time dependency of the effect of thioperamide indicated that the drug acts on mechanisms involved in memory consolidation. Conclusions: The present findings demonstrate that the pro-cognitive effect of thioperamide is probably due to the modulation of post-acquisition memory processes through an action on the cholinergic basal forebrain. Our results indicate also that H₃-antagonists may provide a useful approach for improving spatial recognition memory.