Extracellular serotonin (5-ht) levels in the lateral hypothalamus (lh) after tryptophan injection in normal, obese, weight reduced obese and diet resistant rats

Abstract

Extracellular 5-HT level in the LH was examined using the in. vivo microdialysis technique. Female Spraguc-Dawlcy rats (100 gm) were given either a basal diet (5% fat) or a high (30%) fat diet. In two to three months, 75% of the rats fed the high fat diet became obese (gained more weight than the highest weight gainer of the low fat group). Half of the obese rats (DIO) were then switched to the low fat diet until their cumulative weight gain was less than that achieved by the highest weight gainer of the control group [weight reduced obese (WRO)]. Those rats remained lean on a high fat diet were diet resistant (DR). AU rats then received guide cannuU implantation. On test days, a dialysis probe (2 nun, perfused with artificial cerebrospinal fluid at 1.5 ul/min) was inserted through the implanted guide carmula 3 hours before treatment. Each rat, on separate days, received saline, tryptophan (75 mg/kg) or dexfenfluramine (2 mg/kg) intraperitoneally and perfusates (30 min aliquots) were collected for a period of 210 min. Serotonin and its metabolite 5-hydroxyindoleacetic acid were determined eleclrochcmically after HPLC separation. The two indole levels just before injection were averaged and taken as the baseline level for that day. Subsequent changes in level were expressed as percent of baseline. ANOVA with repeated measures revealed a significant interaction between rat group and treatment (p<0.05). Extracellular 5-HT levels in the LH increased after tryptophan hi both control and DR rats but not in DIO and WRO ran. These findings suggest obesity reduces central serotonergic tone and this effect persists even after the normalization of body weight in the DIO rats.