Ameliorative effects of histamine on 7-chlorokynurenic acid-induced spatial memory deficits in rats.
BACKGROUND
Histamine plays an important role in modulating acquisition and retention in learning and memory process in experimental animals.


OBJECTIVE
We examined the effects of polyamine and histamine on the N-methyl- d-aspartate (NMDA) receptor glycine site antagonist 7-chlorokynurenic acid-induced spatial memory deficits in radial maze performance in rats.


METHODS
Effects of histamine (0.5 or 1 nmol/site intracerebroventricularly), spermidine (1 nmol/site, intracerebroventricularly) and spermine (1 nmol/site, intracerebroventricularly) on spatial memory deficit in 9-week-old-male Wistar rats were observed. Both reference and working memory errors occurred in radial maze performance in rats, following intracerebroventricular injection of 7-chlorokynurenic acid (10 nmol/site).


RESULTS
Spermidine (1 nmol/site, intracerebroventricularly) or spermine (1 nmol/site, intracerebroventricularly) antagonized 7-chlorokynurenic acid-induced deficits on working memory but not on reference memory errors. Intracerebroventricular histamine (0.5 or 1 nmol/site) or thioperamide (100 nmol/site) also ameliorated 7-chlorokynurenic acid-induced working memory deficits. To determine whether the effects of histamine involve histamine receptors, the effects of some methylhistamines were examined. The effects of R-alpha-methylhistamine on radial maze performance were mimicked by histamine. N(alpha)-methylhistamine had no effect on 7-chlorokynurenic acid-induced memory deficits, whereas 1-methylhistamine, but not 3-methylhistamine reversed 7-chlorokynurenic acid-induced working memory deficits.


CONCLUSIONS
These results suggest that the amelioration of 7-chlorokynurenic acid-induced working memory deficits by histamine may involve a direct action of histamine at the polyamine sites on NMDA receptors.
Nishiga
Miyuki
M
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan.
Kamei
Chiaki
C
D000818:Animals; D018691:Excitatory Amino Acid Antagonists / Q000633:toxicity*; D006632:Histamine / Q000494:pharmacology*; D007736:Kynurenic Acid / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000633:toxicity*; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced*; D008761:Methylhistamines / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D011073:Polyamines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013095:Spermidine / Q000494:pharmacology; D013096:Spermine / Q000494:pharmacology
D018691:Excitatory Amino Acid Antagonists; D008761:Methylhistamines; D011073:Polyamines; D016194:Receptors, N-Methyl-D-Aspartate; D013096:Spermine; D006632:Histamine; D007736:Kynurenic Acid; C057013:7-chlorokynurenic acid; D013095:Spermidine