Serotonin type-2 receptor mediated regulation of substance P release in the ventral spinal cord and the effects of chronic antidepressant treatment

Abstract

Regulation of the release of substance P (SP) by the coexisting neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) in the ventral spinal cord and the effects of chronic antidepressant treatment mediated changes in serotonin metabolism on the regulation, were examined. The K+ (40 mmol/l) evoked release of (SP) from slices of the ventral spinal cord of the rat was potentiated by (5-HT) applied to 100 mumol/l concentration. This effect was blocked by the serotoninergic antagonists methysergide (10 mumol/l), methiotepin (10 mumol/l) and fully blocked by ketanserin (10 mumol/l). Thus the 5-HT receptor which regulates the release of SP appears to belong to the type-2 5-HT receptors. Chronic treatment with the selective serotonin uptake inhibitor zimelidine (14 days, 2 X 10 mumol/kg/day, p.o.) lowered the tissue levels of the 5-HT metabolite: 5-hydroxyindol acetic acid (5-HIAA) and elevated the tissue levels of SP in both the ventral and dorsal spinal cord as compared to that in the vehicle treated group (14 days, 2 X 5 ml saline/kg/day, p.o.). The decrease in the 5-HIAA levels after chronic zimelidine treatment was quantitatively similar in the dorsal (33%, p less than 0.01) and ventral (31%, p less than 0.05) spinal cord. The increase in SP levels after chronic zimelidine treatment was more pronounced in the ventral cord (80%, p less than 0.01) where the majority of the SP containing nerve endings also contain 5-HT, than in the dorsal spinal cord (22% increase in SP, p less than 0.05), where only a minor fraction of the SP-containing nerve endings shows a 5-HT/SP coexistence.(ABSTRACT TRUNCATED AT 250 WORDS)