Cholinergic and glutamatergic activation reverses working memory failure by hippocampal histamine H1 receptor blockade in rats.
Intrahippocampal administration of the histamine H1 receptor antagonist pyrilamine (3.2-32 ug/ side) but not the histamine H2 receptor antagonist cimetidine (1.0-10 microg/side) increased the number of errors in the working memory task with a three-panel runway setup. The increase in working memory errors induced by intrahippocampal 32 microg/side pyrilamine was significantly reduced by concurrent infusion of the histamine H1 receptor agonist 2-pyridylethylamine (3.2 and 10 microg/side). The cholinesterase inhibitor physostigmine ( 1.0 and 3.2 microg/side) and D-cycloserine (0.32 and 1.0 microg/side), the partial agonist at the glycine binding site on the NMDA receptor/channel complex, reduced the increase in working memory errors induced by intrahippocampal 32 microg/side pyrilamine. These results suggest that the hippocampal histaminergic activity via histamine H1 receptor is necessary for normal working memory processes and that the septohippocampal cholinergic activation and positive modulation of the NMDA receptor/channel through activation of the glycine site can alleviate dysfunction of hippocampal histamine H1 receptor-mediated neurotransmission involved in working memory function.
Nakazato
E
E
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Yamamoto
T
T
Ohno
M
M
Watanabe
S
S
D000109:Acetylcholine / Q000502:physiology*; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology*; D003523:Cycloserine / Q000494:pharmacology; D004347:Drug Interactions; D018698:Glutamic Acid / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D017442:Histamine Agonists; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D008297:Male; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy; D009474:Neurons / Q000502:physiology; D010830:Physostigmine / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011738:Pyrilamine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011969:Receptors, Histamine H1 / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000502:physiology
D002800:Cholinesterase Inhibitors; D017442:Histamine Agonists; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D011725:Pyridines; D011969:Receptors, Histamine H1; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D002927:Cimetidine; D003523:Cycloserine; D010830:Physostigmine; C006183:2-(2-aminoethyl)pyridine; D011738:Pyrilamine; D000109:Acetylcholine