Changes in extracellular PVN monoamines and macronutrient intake after idazoxan or fluoxetine injection

Norepinephrine (NE) and serotonin (5-HT) in the paraventricular nucleus (PVN) have opposite effects on feeding, with NE stimulating carbohydrate intake through alpha 2 noradrenergic receptors and 5-HT inhibiting carbohydrate intake. This study examined the action of drugs that affect brain monoaminergic systems, in terms of their impact on nutrient intake and on PVN monoamines measured using microdialysis. The drugs studied were idazoxan, a blocker of alpha 2 receptors, or fluoxetine, a 5-HT reuptake blocker. In rats maintained on pure macronutrient diets, idazoxan (1 mg/kg) and fluoxetine (10 mg/kg), 120 min after injection both reduced total food intake, and specifically carbohydrate intake. In dialysis experiments, successive 20-min dialysate samples were taken, three samples before and seven samples after intraperitoneal injection of idazoxan (5 and 20 mg/kg), fluoxetine (10 mg/kg), or vehicle. Idazoxan increased NE, homovanillic acid, and dihydroxyphenylacetic acid in the PVN. Fluoxetine induced a significant increment of 5-HT in PVN, while producing a smaller increase in NE, dopamine, and homovanillic acid. These results support the conclusion that the impact of these drugs on macronutrient intake may be a consequence of their action on endogenous monoamine systems in the PVN. Thus, in this nucleus, the blockade of alpha 2-noradrenergic receptors, like stimulation of 5-HT receptors, attenuates normal ingestion of carbohydrate.