Effect of endogenous histamine in the ventral hippocampus on fear memory deficits induced by scopolamine as evaluated by step-through avoidance response in rats.
In the present study, the effects of endogenous histamine in the ventral hippocampus on fear memory deficits induced by scopolamine were investigated as evaluated by step-through avoidance response in adult male rats. Bilateral ventral hippocampal injection of scopolamine (i.h., 2, 5 microg/site) significantly produced depressant effects on the active avoidance response in a dose-dependent manner. Histamine H(3)-antagonist clobenpropit (5, 10 microg/site) significantly ameliorated the fear memory deficits induced by scopolamine in a dose-dependent manner. Its procognitive effect was completely antagonized by immepip (10 microg/site), a selective histamine H(3)-agonist. Both histamine H(1)-antagonist pyrilamine and H(2)-antagonist cimetidine, also inhibited the procognitive effects of clobenpropit. Additionally, the procognitive effects of clobenpropit on the fear memory deficits induced by scopolamine were significantly potentiated by intraperitoneal (i.p.) injection of histidine, a precursor of histamine, but markedly reversed by i.h. injection of alpha-fluoromethylhistidine (FMH, 10 microg/site), a selective and potent histidine decarboxylase inhibitor. It is concluded that the increased endogenous histamine release in the ventral hippocampus ameliorates the scopolamine-induced fear memory deficits, and its action is mainly mediated by histamine presynaptic H(3)-receptors and postsynaptic H(1)- and H(2)-receptors.
Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou, China 310031.
Chaoyang
C
Yu
Yao
Y
Shen
Lisha
L
Xu
Yuanyuan
Y
Zhu
Zhenbin
Z
Zhuge
Yuwen
Y
Huang
Timmerman
T
Henk
Leurs
L
Rob
Erqing
E
Wei
Zhong
Z
Chen
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005239:Fear / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D006632:Histamine / Q000378:metabolism*; D017442:Histamine Agonists / Q000008:administration & dosage; D006633:Histamine Antagonists / Q000008:administration & dosage; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D008569:Memory Disorders / Q000139:chemically induced*; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology*; D012601:Scopolamine
D017442:Histamine Agonists; D006633:Histamine Antagonists; D006632:Histamine; D012601:Scopolamine