Functional consequences of unilateral lesion of the locus coeruleus: A quantitative [ 14C]2-deoxyglucose investigation

Abstract

The functional consequences, as reflected in local rates of glucose utilization, of ablation of the locus coeruleus (the nucleus from which a major portion of the ascending noradrenergic fibres arise) have been examined in conscious rats with the quantitative autoradiographic [ 14C]2-deoxyglucose technique. Measurements of glucose utilization were made 72 h after histologically verified unilateral electrolytic lesions of the locus coeruleus. In the overwhelming majority of the 35 grey matter regions examined, the rate of glucose utilization was unaltered by lesions of the locus coeruleus, and in the limited number of CNS regions in which significant alterations were observed, the magnitude of the changes was invariably modest (less than 20% different from sham-operated control animals). Reductions in glucose use were observed in ipsilateral ventral (by 14%) and lateral thalamic nuclei (by 17%), and rates of glucose utilization in most regions of cerebral cortex were significantly lower (about 10%) in the ipsilateral hemisphere relative to the hemisphere contralateral to the lesion. In one region, the median raphe nucleus, glucose utilization was significantly elevated (by 19%) following lesions of the locus coeruleus. Attempts to accentuate the effects of locus coeruleus lesions by pharmacological manipulation of CNS adrenoreceptors by means of the systemic administration of phenoxybenzamine (30 mg/kg, 40 min prior to measurement of glucose use) in animals bearing unilateral locus coeruleus lesions were unsuccessful; the modest alterations in glucose utilization observed following locus coeruleus lesion alone were even less pronounced in lesioned animals receiving phenoxybenzamine. The alterations in local glucose utilization provoked by phenoxybenzamine were similar in sham-lesioned and locus coeruleus-lesioned animals. It would appear that the functional consequences, in terms of glucose utilization, are much less pronounced when a single neurotransmitter system (in the present studies, noradrenergic neurones) is lesioned than when a multiple neurotransmitter, functionally integrated pathway (such as the visual system) is disrupted.