Activation of hypothalamic insulin by serotonin is the primary event of the insulin-serotonin interaction involved in the control of feeding

In previous experiments, we reported a close parallelism in the responses o f both serotonin (5-HT) and insulin in the hypothalamic PVN-VMH region of f reely-moving rats during feeding. Thus, hypothalamic 5-HT and insulin may p articipate, independently or in interaction, in the control of carbohydrate and fat ingestion. The precedence of the activation of one or the other su bstance remained to be investigated. In adult male Wistar rats, (a) dexfenf luramine was administered to the PVN-VMH region by reverse microdialysis (8 0 mu M for 10 min) while local insulin was assessed; (b) insulin was locall y infused (400 mU for 10 min) through the tip of the dialysis probe while 5 -HT was measured. Dexfenfluramine immediately increased 5-HT release, and a lso extracellular insulin levels (+102%). This activation of insulin by ser otonin is actually a central effect since neither insulinemia nor glycemia were affected. Conversely, insulin enhanced 5-HT release (+81%), but only 4 5 min after the beginning of its infusion. Noradrenaline, dopamine and meta bolites mere slightly or not at all modified by insulin. These data demonst rate that an interaction does exist between insulin and 5-HT in the VMH-PVN area. Because of the delay of 5-HT response to insulin, an activation of t he serotonergic system would be the causal event acting immediately on insu lin: and not the contrary. Whatever the exact mechanism of this interaction , it seems to be a link in a larger cascade of events involving numerous ne urotransmitters and peptides leading to the regulation of feeding. (C) 2000 Elsevier Science B.V. All rights reserved.