Cholinergic and serotonergic neocortical projection lesions given singly or in combination cause only mild impairments on tests of skilled movement in rats: evaluation of a model of dementia

Abstract

The cholinergic (ACh) projections of the nucleus basalis and the serotonergic (5-HT) projections of the raphe nuclei to the neocortex are required for the normal function of the neocortex. Nevertheless, damage to either system alone has little effect on the behavior of rats, but conjoint damage to both systems is reported to produce dementia to the point that animals are described as being unable to engage in intelligent behavior. Because rats with bilateral damage to both systems are so severely impaired, they are not useful for chronic studies. The objective of the present research was to determine whether unilateral depletions produce a functional impairment. Rats received unilateral neurotoxic lesions to either the nucleus basalis (quisqualic acid), or the medial forebrain bundle (5,7-dihydroxytryptamine), or both, which reduced neocortical levels of ACh (55%) and 5-HT (63%). The rats then received a battery of tests sensitive to unilateral neocortical injury. The 5-HT lesion produced no quantitative or qualitative deficits on reaching for food, walking across a horizontal ladder, forelimb placement in a cylinder, sensory detection of adhesive paper applied to the wrists, or forelimb inhibition during swimming. The ACh lesion produced mild qualitative deficits in reaching. Combined lesions produced mild deficits in skilled reaching, ladder walking, and sensory detection. In contrast to the mild impairments produced by the lesions, pharmacological blockade of either ACh with atropine or 5-HT with methiothepin mesylate systemically blocked skilled motor behavior as assessed by skilled reaching. The results are discussed in relation to the problems associated with the development of a unilateral model of dementia.