Differential effects of physostigmine and pilocarpine on the spatial memory deficits produced by two septo-hippocampal deafferentations in rats.

Abstract

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.

• Authors: N Matsuoka, N Maeda, Y Ohkubo, I Yamaguchi
• Journal: Brain research (Brain Res) Vol. 559 Issue 2 Pg. 233-40 (Sep 20 1991) ISSN: 0006-8993 [Print] Netherlands
• PMID: 1794099 (Publication Type: Journal Article)

Chemical References

• Pilocarpine
• Physostigmine
• Choline O-Acetyltransferase

Topics

• Animals
• Choline O-Acetyltransferase (metabolism)
• Hippocampus (cytology, enzymology, physiology)
• Male
• Memory Disorders (physiopathology)
• Neurons, Afferent (physiology)
• Physostigmine (pharmacology)
• Pilocarpine (pharmacology)
• Rats
• Rats, Inbred F344
• Space Perception (drug effects)
• Stereotaxic Techniques