Influence of histamine depletion on learning and memory recollection in rats.
To clarify the role of endogenous histamine in learning and memory, the effect of alpha-fluoromethylhistidine on active avoidance response in rats was studied. alpha-Fluoromethylhistidine (20-100 mg/kg or 10-50 micrograms) significantly (P < 0.05 or P < 0.01) prolonged the response latency in active avoidance response when administered by either intraperitoneal or intracerebroventricular injection. These effects were dose-related and long lasting. A prolongation of the response latency induced by an intraperitoneal injection of alpha-fluoromethylhistidine (100 mg/kg) was antagonized by intracerebroventricular injection of histamine (10 and 20 ng) in a dose-dependent manner. In addition, the acquisition of this response was retarded by a consecutive intracerebroventricular injection of alpha-fluoromethylhistidine (50 micrograms), whereas histamine (100 ng) facilitated the response acquisition when administered by the same route. Both intraperitoneal (100 mg/kg) and intracerebroventricular injection of alpha-fluoromethylhistidine (50 micrograms) significantly (P < 0.05 or P < 0.01) decreased the brain histamine content, especially in the hippocampus and hypothalamus. When alpha-fluoromethylhistidine (50 micrograms) was injected intracerebroventricularly, there is a high correlation between a prolongation of the response latency and a decrease in histamine content of these brain areas. Based on these findings, it was concluded that an intimate relation may exist between a prolongation of response latency in the active avoidance response and a decrease in the brain histamine content; endogenous histamine may play an important role in learning and memory recollection in rats.
Kamei
C
C
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Okumura
Y
Y
Tasaka
K
K
D000818:Animals; D001259:Ataxia / Q000139:chemically induced / Q000523:psychology; D001362:Avoidance Learning / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005106:Exploratory Behavior / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006632:Histamine / Q000502:physiology*; D006640:Histidine Decarboxylase / Q000037:antagonists & inhibitors; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008297:Male; D011939:Mental Recall / Q000187:drug effects*; D008762:Methylhistidines / Q000008:administration & dosage / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D008762:Methylhistidines; C028309:alpha-fluoromethylhistidine; D006632:Histamine; D006640:Histidine Decarboxylase