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Histamine H3-receptor blockade in the rat nucleus basalis magnocellularis improves place recognition memory
M Orsetti1, C Ferretti, RicciS Gamalero
1Dipartimento di Scienze C.A.F. e Farmacologiche, Università del Piemonte Orientale, Viale F. Ferrucci 33, 28100 Novara, Italy.
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 microl; 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 microl; post-acquisition treatment), or 2 min prior to the second trial (1.5, 7.5, and 37.5 ng/0.5 microl; 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 H(3)-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.
