Differential effects of physostigmine and pilocarpine on the spatial memory deficits produced by two septo-hippocampal deafferentations in rats.
Rats that had received two kinds of septo-hippocampal deafferentations, medial septum (MS) lesion and fimbria-fornix (FF) transection, were assayed for brain cholineacetyltransferase (ChAT) activity and spatial memory in an 8-arm radial maze task. Both lesions produced profound and long-lasting spatial memory impairments, which were characterized by a reduction in the numbers of correct arm choices and first correct choices, a reduction in the percent of correct choices and an increase in the number of errors. The degree of memory impairment was severer in FF- than in MS-lesioned rats, and paralleled that of decreases in ChAT activity in the hippocampus. MS lesion reduced ChAT activity in the hippocampus by approximately 45%, while FF lesion almost completely depleted the activity. An intraperitoneal injection of physostigmine (0.0032-0.32 mg/kg), an acetylcholinesterase (AChE) inhibitor, significantly ameliorated the spatial memory deficit induced by MS lesion, but hardly affected that by FF lesion. In contrast, intraperitoneal doses (0.032-3.2 mg/kg) of pilocarpine, a muscarinic agonist, showed a significant improvement of both types of memory deficit with bell shaped dose-response curves. The drug was more potent in the FF- than in the MS-lesioned rats. These results suggest that the septo-hippocampal cholinergic system plays a crucial role in the maintenance of spatial memory, and that the degree of septo-hippocampal deafferentation affects the efficacy of cholinergic drugs.
Matsuoka
N
N
Tsukuba Research Laboratories, Fujisawa Pharmaceutical Co. Ltd., Ibaraki, Japan.
Maeda
N
N
Ohkubo
Y
Y
Yamaguchi
I
I
D000818:Animals; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000201:enzymology / Q000502:physiology*; D008297:Male; D008569:Memory Disorders / Q000503:physiopathology*; D009475:Neurons, Afferent / Q000502:physiology*; D010830:Physostigmine / Q000494:pharmacology*; D010862:Pilocarpine / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D013028:Space Perception / Q000187:drug effects*; D013238:Stereotaxic Techniques
D010862:Pilocarpine; D010830:Physostigmine; D002795:Choline O-Acetyltransferase