Adrenalectomy increases serotonin turnover in brains of obese Zucker rats

Abstract

Because adrenalectomy tends to normalize many metabolic abnormalities of obese Zucker rats, we hypothesized that it would also normalize the depressed serotonergic turnover in their ventromedial nucleus (VMN). Lean (Fa/Fa) and obese (fa/fa) male Zucker rats were adrenalectomized or sham operated when 5 wks old and sacrificed at 11 wks. Their brains were frozen, and 13 areas were dissected for HPLC-EC analysis of monoamines and metabolites. Consistent with previous studies, VMN serotonin turnover (indexed by 5-HIAA/5-HT) was lower in obese than lean sham-operated rats. Monoamine and metabolite concentrations were altered in several other brain areas as well. Adrenalectomy reduced percent body fat and elevated VMN serotonergic turnover more in obese than in lean rats. It also stimulated serotonergic turnover in almost every brain area examined. We conclude that in obese Zucker rats: monoaminergic activity is altered in several brain areas involved in regulating energy balance; adrenalectomy normalizes the reduced VMN serotonergic turnover seen in the obese rats; and adrenalectomy results in a generalized increase in central serotonergic turnover. These data are consistent with serotonin's role in inhibiting food intake and enhancing sympathetic stimulation of energy metabolism.