Metergoline potentiates natural feeding and antagonizes the anorectic action of medial hypothalamic 5-hydroxytryptamine

Abstract

Medial hypothalamic injections of 5-hydroxytryptamine (5-HT) or its agonists have been reported to inhibit feeding elicited by norepinephrine (NE), suggesting that these two transmitter systems interact antagonistically in the control of ingestive behavior. The present study was designed to directly test the hypothesis that 5-HT inhibits adrenergic feeding, specifically at the onset of the rat's nocturnal eating cycle. Free-feeding animals were injected with 5-HT (5–20 nmol) immediately before NE (20 nmol) and food intake was measured 1.5 h postinjection. In separate groups of rats, the serotonergic antagonist metergoline (MET) (2.5–20 nmol) was injected into the paraventricular nucleus (PVN) immediately before 5-HT, or before combined injections of 5-HT and NE. The feeding-stimulant action of MET alone, injected IP (0.25–2 mg/kg) or centrally (2.5–40 nmol), was also examined. Results indicated that administration of 5-HT into the PVN suppressed dark onset feeding and dose-dependently blocked NE-stimulated eating. Pretreatment with MET attenuated the inhibitory action of 5-HT on feeding, and reversed the serotonergic blockade of the adrenergic eating response. Further, systemically injected MET significantly increased dark onset feeding, whereas PVN injections failed to alter food intake reliably. These findings provide the first direct evidence that serotonergic and adrenergic systems within the PVN interact in a competitive manner to modulate the natural high rates of feeding displayed by rats during the early dark period. Although MET effectively blocked the anorectic effect of 5-HT, the feeding-stimulant action of this compound alone does not appear to be mediated within the PVN.