Participation of hippocampal ionotropic glutamate receptors in histamine H(1) antagonist-induced memory deficit in rats.
BACKGROUND
Pyrilamine, a selective histamine H(1) antagonist, impaired spatial memory, and decreased hippocampal theta activity during a radial maze task.


OBJECTIVE
We investigated the ameliorative effects of glutamatergic drugs on pyrilamine-induced spatial memory deficit and the decrease in hippocampal theta activity in rats.


METHODS
Drug effects were measured using an eight-arm radial maze with four arms baited. Hippocampal theta rhythm during the radial maze task was also recorded with a polygraph system using a telemetric technique.


RESULTS
Intraperitoneal injection of pyrilamine (35 mg/kg) resulted in impaired reference and working memory in the radial maze task and a decrease in the amplitude and power of hippocampal theta waves. The working memory deficit and the decrease in hippocampal theta power were antagonized by intrahippocampal injection of D: -cycloserine (1 microg/side), spermidine (10 microg/side), spermine (10 microg/side), aniracetam (1 microg/side), and 1-(1,3-benzodioxol-5-ylcarbonyl) piperidine (1-BCP) (1 microg/side), but not concanavalin A.


CONCLUSIONS
These results clearly indicate that H(1) antagonist-induced working memory deficit, and the decrease in hippocampal theta activity was closely associated with hippocampal glutamatergic neurotransmission mediated by N-methyl-D: -aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors.
Masuoka
Takayoshi
T
Department of Medicinal Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 700-8530, Japan.
Saito
Shunsuke
S
Kamei
Chiaki
C
D000818:Animals; D003208:Concanavalin A / Q000494:pharmacology; D003523:Cycloserine / Q000494:pharmacology; D004149:Dioxoles / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects; D005583:Fourier Analysis; D006624:Hippocampus / Q000187:drug effects*; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D007267:Injections; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D011939:Mental Recall / Q000187:drug effects*; D009949:Orientation / Q000187:drug effects*; D010880:Piperidines / Q000494:pharmacology; D011738:Pyrilamine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000187:drug effects*; D011969:Receptors, Histamine H1 / Q000187:drug effects*; D018092:Kainic Acid Receptors / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D012815:Signal Processing, Computer-Assisted; D013095:Spermidine / Q000494:pharmacology; D013096:Spermine / Q000494:pharmacology; D013826:Theta Rhythm; D000097806:GluK2 Kainate Receptor
D003208:Concanavalin A; D003523:Cycloserine; D004149:Dioxoles; D006634:Histamine H1 Antagonists; D010880:Piperidines; D011738:Pyrilamine; D011760:Pyrrolidinones; D018091:Receptors, AMPA; D011969:Receptors, Histamine H1; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D013095:Spermidine; D013096:Spermine; D000097806:GluK2 Kainate Receptor; C085415:1-(1,3-benzodioxol-5-ylcarbonyl)piperidine; C036466:aniracetam