Influence of ascending serotonergic pathways on glucose use in the conscious rat brain. I. Effects of electrolytic or neurotoxic lesions of the dorsal and/or median raphé nucleus.

The regional cerebral metabolic effects of manipulations of the central serotonergic pathways are largely unknown. To address this topic, we have examined the consequences of electrolytic lesions of the rostral (median and/or dorsal) raphé nuclei on local cerebral glucose utilization (CMRglu) in the unanaesthetized rat brain. These studies were complemented by comparing control rats to rats that received prior intraventricular administration of the serotonergic neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT). CMRglu was determined in 56 neuroanatomically defined regions of the central nervous system in lightly restrained rats, by the quantitative autoradiographic 2-deoxyglucose technique. In all, 6 groups of rats were studied: sham-lesioned rats, rats with electrolytic lesion of the median, dorsal, or both these raphé nuclei; sham-injected and 5,7-DHT pretreated rats. The efficacy of both electrolytic and neurotoxic lesions was verified, in each animal, by neurochemical microassay of 5-hydroxytryptamine and its metabolite in samples of striatum, hippocampus and prefrontal cortex. Chronic interruption of serotonergic transmission was remarkable for the lack of resultant change in CMRglu. In rats that were subjected to electrolytic lesions of both median and dorsal raphé nuclei, discrete and significant decreases in CMRglu were observed in the red nucleus, substantia nigra and inferior olivary nucleus only. The rats subjected to 5,7-DHT treatment displayed no significant changes in CMRglu in all the brain regions analyzed, despite an 80% decrease in the concentrations of endogenous 5-hydroxytryptamine. Thus, it would appear that a viable serotonergic transmission is not a major determinant of integrated functional activity, even in those brain structures that receive rich raphé projections. Two hypotheses are advanced for this lack of change: firstly, the chronic reduction of 5-hydroxytryptamine levels is accompanied by compensatory changes in this or other neurotransmitter systems; secondly, serotonergic neurones may exert a phasic--rather than tonic--influence on glucose use in the mammalian brain.