Histamine H3-receptor blockade in the rat nucleus basalis magnocellularis improves place recognition memory.
BACKGROUND
Several lines of evidence have indicated that the central histaminergic system might be involved in learning and memory


OBJECTIVE
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.
Orsetti
M
M
Dipartimento di Scienze C.A.F. e Farmacologiche, Università del Piemonte Orientale, Viale F. Ferrucci 33, 28100 Novara, Italy.
Ferretti
C
C
Gamalero
RicciS
R
Ghi
P
P
D000818:Animals; D020532:Basal Nucleus of Meynert / Q000187:drug effects* / Q000502:physiology*; D006633:Histamine Antagonists / Q000494:pharmacology*; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018100:Receptors, Histamine H3 / Q000378:metabolism* / Q000502:physiology; D021641:Recognition, Psychology / Q000187:drug effects / Q000502:physiology*
D006633:Histamine Antagonists; D010880:Piperidines; D018100:Receptors, Histamine H3; C052075:thioperamide