The Effect of Electrical Stimulation of the Dorsal Raphe Nucleus on Local Cerebral Glucose Metabolism and Epileptogenesis in the Rat
Anatomic connections between the dorsal raphé and the hippocampus have been described in the literature; however, the understanding of the functional importance of these connections is not complete. In these studies the "functional" raphé-hippocampal pathway was elucidated first by the 2-deoxy-d-glucose (2-DG) method, and second by the effect of dorsal raphé electrical stimulation on kindled seizure in the rat. In the 2-DG study, differences in local rates of cerebral glucose metabolism were quantified. The pattern of 2-DG uptake differed significantly from controls (animals with electrodes placed and not receiving an electrical stimulus) and subjects stimulated in the pontine oral reticular formation. The dorsal hippocampus CA1&2 responded with an increase over control values of 87%, dorsal hippocampus CA3&4 of 68%, the dentate gyrus of 83%, ventral hippocampus: CA1&2 of 71% and CA3&4 of 67% (p ≤ 0.01). This study thus showed that the dorsal hippocampus responds to dorsal raphé stimulation more readily than the ventral hippocampus, and that the lacunosum-moleculare layer of the dorsal hippocampus had a significant increase in metabolic rate following dorsal raphé electrical stimulation. Among extrahippocampal structures, the nucleus accumbens had the highest value for glucose uptake during dorsal raphé stimulation, an increase over controls of 118%. Other structures showing marked increase in glucose metabolism were: the medial forebrain bundle(MFB) = 68%, the cingulate bundle = 54%, the lateral septal nucleus = 41%, the diagonal band of Broca = 31%, the reticular thalamic nucleus = 49%, and the dorsal medial amygdaloid nucleus = 23% (p ≤ 0.01). pontine oral reticular formation (PORF) 2-DG uptake patterns were markedly different from dorsal raphé stimulated and control animals. Kindled animals also exhibited specific changes in various seizure indices that are related to the efficacy of seizure inhibition. Hippocampal kindled animals revealed an increase in afterdischarge threshold, a decrease in seizure severity, a decrease in seizure duration, and a greater number of stimulations required to generate afterdischarges. Dorsal raphé-stimulated-amygdala-kindled animals showed similar changes in seizure indices from control animals but the inhibitory effect was not as great as the dorsal raphé effect on hippocampal-kindled seizures. Moreover, dorsal raphé electrical stimulation generally decreased the postictal period of behavioral depression.
Endocrinology, Diabetes, and Metabolism, Physiology, Raphé Nuclei -- physiology; Electric Stimulation; Hippocampus -- physiology; Glucose -- metabolism; Epilepsy -- etiology
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