title: Ameliorative effects of histamine on 7-chlorokynurenic acid-induced spatial memory deficits in rats.
abstract: 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.
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Nishiga
authors.forename: Chiaki
authors.initials: C
authors.lastname: Kamei
mesh_terms: 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
chemical_list: 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