Influence of ascending serotonergic pathways on glucose use in the conscious rat brain. II. Effects of electrical stimulation of the rostral raphé nuclei

Abstract

Although lesions of the rostral raphé nuclei have minimal effects on integrated functional activity, as studied by the 2-deoxyglucose technique, the repercussions of activating the ascending serotonergic pathways have yet to be reported in the literature. To examine this question, we studied the consequences of the electrical stimulation of the rostral (median or dorsal) raphé nuclei on local cerebral glucose use in the conscious rat. Glucose use was determined by quantitative autoradiography in 105 defined brain structures. Raphé stimulation increased glucose utilization in a number of well-defined structures and pathways, dorsal raphé stimulation being systematically more effective than median raphé stimulation. Of all the neocortical regions studied, only the somatosensory cortex displayed a columnar and laminar pattern of increased glucose use that was restricted to the somatotopic delineation of the rat's head and face. Increased glucose use was seen in almost all key elements of the extrapyramidal system with the notable exception of the caudate-putamen. The thalamic nuclei that were activated by rostral raphé stimulation included those that subserve the processing of someethetic, accessory visual and limbic information. Raphé stimulation-induced decreases in local cerebral glucose use were never observed. Almost all of the induced changes could be prevented or obtunded by prior intraventricular administration of the serotonergic neurotoxin 5,7-dihydroxytryptamine, suggesting that the majority of the raphé-induced changes in integrated functional activity were mediated via the activation of serotonergic neurones. The magnitude and pattern of the increases in glucose use could not always be correlated with the regional density of serotonergic innervation nor with the distribution of 5-hydroxytryptamine receptor subtypes in the adult brain. However, the pattern of increased cortical glucose use closely matches the selective serotonergic innervation of the somatosensory cortex found in early postnatal development. Thus, it would appear that the 2-deoxyglucose technique reveals functional units in the cortex that are innervated at an early ontogenic stage. We postulate tht the discrete and highly organized in integrated functional activity that follow raphé stimulation are due to serotonin acting in a phasic manner on restricted, possibly specialized, postsynaptic structures. Finally, the widespread changes in glucose use that are revealed by rostral raphé stimulation, when considered along with the near-absence of effect following raphé lesions, would again suggest that ascending serotonergic neurones exert a phasic — rather than tonic — influence on integrated functional activity in the mammalian brain.