Effects of systemic 8-OH-DPAT on the feeding induced by hypothalamic NE infusion

Abstract

Past research suggests that activating brain serotonin (5-hydroxy-tryptamine or 5-HT) systems can inhibit feeding induced by activating brain norepinephrine (NE) systems. To explore this interaction more fully, we tested the capacity of the endogenous 5-HT release inhibitor, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), to enhance feeding stimulated by infusing NE into the medial hypothalamus. All experiments were conducted using ad lib-fed adult male rats with indwelling cannulae aimed at the paraventricular nucleus (PVN). In the first study, proven PVN-NE responders were tested for 40-min food intake after receiving 20 nanomoles (nmol) 1-NE or saline in the PVN following subcutaneous (SC) pretreatment with 250 μg/kg 8-OH-DPAT or saline. Both drugs produced equivalent, reliable increments in feeding compared to PVN-saline. However, no additivity or synergy was seen when they were combined. Short-term water intake was unaffected by these treatments as was subsequent food or water intake over the next 22 hr. In a second study, additional proven PVN-NE responders were tested under two comparable conditions when 1) the 8-OH-DPAT dose was left at 250 μg/kg but the NE dose was lowered to 10 nmol, and 2) the 8-OH-DPAT dose was lowered to 120 μg/kg and the NE dose was increased to 40 nmol. In the first case, no reliable feeding was seen in response to either agent alone or combined. In the second case, NE alone enhanced feeding but 8-OH-DPAT did not. The combination of both produced the same enhanced feeding as seen with NE alone. These findings suggests that it is not possible to enhance the acute food intake elicited by PVN-NE stimulation with systemic 8-OH-DPAT as a second feeding stimulus. Additional work will be needed to confirm the more general implication of this finding, which is that impeding brain 5-HT neurotransmission may not enhance food intake initiated by other processes.