Hypothalamic monoamines measured by microdialysis in rats treated with 2-deoxy-glucose or d-fenfluramine

Abstract

The effects on brain monoamines (norepinephrine, serotonin and the metabolite of dopamine) following administration of d-fenfluramine (10 mg/kg IP) and 2-deoxy-d-glucose (500 mg/kg IP) have been measured by microdialysis from the ventromedial hypothalamus, lateral hypothalamic area and dorsomedial hypothalamus of conscious, unrestrained rats. Following administration of d-fenfluramine there was a significant increase in the concentration of serotonin in the ventromedial hypothalamus and lateral hypothalamic area, but no significant increase in the DMH. 5-HIAA (5-hydroxy-3-indoleacetic acid), the metabolite of serotonin, was increased in the DMH, but not in the other two regions. DOPAC (3,4-dihydroxyphenylacetic acid) was increased following fenfluramine treatment in all three regions examined. An increase in norepinephrine was observed in the VMH, but not in the other two regions, while the concentration of the 3-methoxy-4-hydroxyphenyglycol (MHPG) was increased in both areas. Treatment with 2-deoxy-D-glucose (2DG) was associated with fewer changes. In the lateral hypothalamic area there was a decrease in 5-HIAA and an increase in DOPAC. In the VMH there was an increase in norepinephrine and a decrease in MHPG in the DMH, but otherwise no significant alterations were observed. These data lead to the following conclusions: 1) monoamine concentrations respond differently to injections of fenfluramine and 2-DG; 2) changes in monoamine concentration can be monitored in hypothalamic regions that are less than 1 mm apart; 3) the reduced food intake following injection of fenfluramine is associated with increased serotonin release and/or turnover as well as increased turnover of dopamine; and 4) the stimulation of feeding following 2-deoxyglucose produced no clear changes in monoamines, implying that its biologic basis may involve other neurotransmitters.