CHANGES IN EXTRACELLULAR PVN MONOAMINES AND MACRONUTRIENT INTAKE AFTER IDAZOXAN OR FLUOXETINE INJECTION

Norepinephrine (NE) and serotonin (5-HT) in the paraventricular nucleu s (PVN) have opposite effects on feeding, with NE stimulating carbohyd rate intake through alpha2 noradrenergic receptors and 5-HT inhibiting carbohydrate intake. This study examined the action of drugs that aff ect brain monoaminergic systems, in terms of their impact on nutrient intake and on PVN monoamines measured using microdialysis. The drugs s tudied were idazoxan, a blocker of alpha2 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 tak en, three samples before and seven samples after intraperitoneal injec tion of idazoxan (5 and 20 mg/kg), fluoxetine (10 mg/kg), or vehicle. Idazoxan increased NE, homovanillic acid, and dihydroxyphenylacetic ac id in the PVN. Fluoxetine induced a significant increment of 5-HT in P VN, while producing a smaller increase in NE, dopamine, and homovanill ic 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 b lockade of alpha2-noradrenergic receptors, like stimulation of 5-HT re ceptors, attenuates normal ingestion of carbohydrate.