Enhanced sensitivity of cerebellar Purkinje cells to iontophoretically-applied serotonin in thiamine deficiency

Abstract

Electrophysiological aspects of thiamine depletion in the rat induced by dietary deficiency are described. Behavioral changes as well as qualitative and quantitative alterations in the sensitivity of cerebellar Purkinje cells to iontophoretically-applied 5-hydroxytryptamine (5-HT) were observed. Thiamine-deficient rats were characterized essentially by ataxia, piloerection, paresis, apparent weakness, and hypothermia after 4-6 weeks on a thiamine-free diet. Basal Purkinje cell firing frequency was unaffected by thiamine deficiency. The response of Purkinje cells to iontophoretically-applied 5-HT was solely inhibitory in deficient rats. In control rats, however, responses to 5-HT were excitatory, biphasic, or inhibitory. Neurons in the thiamine-deficient animals were more sensitive to the inhibitory effects of 5-HT, as demonstrated by a significant parallel shift to the left of the dose-response curve. Durations of 5-HT effects were similar in both groups. Dose-response relationships for GABA-induced inhibition of Purkinje cell firing from thiamine deficient and control rats did not differ from one another. These data demonstrate a relatively selective effect of thiamine depletion on cerebellar serotonergic neurotransmission assessed electrophysiologically. We believe there is up-regulation of 5-HT receptors on Purkinje cells caused by thiamine deficiency-induced impairment of indoleamine input to the cerebellum from raphe and related nuclei.