Differential effects of drugs on the behaviour of rats with selective fimbria-fornix lesions and intrahippocampal septal cell transplants

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.