Disruption of central cholinergic systems in the rat by basal forebrain lesions or atropine: effects on feeding, sensorimotor behaviour, locomotor activity and spatial navigation

Abstract

Rats with ibotenic acid lesions of the nucleus basalis magnocellularis, the origin of the extrinsic cholinergic innervation of the cortex, were examined for changes in feeding, sensorimotor behaviour, nocturnal locomotor activity, and place navigation in the Morris swimming pool task, in comparison with control rats and rats receiving the muscarinic antagonist, atropine. The lesions produced acute feeding impairments, marked by weight loss and vigorous active rejection of food and water lasting 2-4 days, sensorimotor impairments in placing and orienting, and overnight hyperactivity. A similar hyperactivity was induced by atropine, lasting approximately 6 h following the injection. Rats with lesions or receiving atropine were similarly impaired in the acquisition of the spatial navigation task, they failed to reach control levels of efficiency even once they had acquired the task, and they showed small but significant retention impairments when pretrained in the absence of either treatment. The results are discussed in terms of the lesions producing a disruption of cortical cholinergic systems, with implications for the clinical disorder of senile dementia of the Alzheimer type, and in terms of possible associated disruption to non-cholinergic systems.