ADMINISTRATION OF 8-OH-DPAT INTO THE MIDBRAIN RAPHE NUCLEI - EFFECTS ON MEDIAL HYPOTHALAMIC NE-INDUCED FEEDING

The 5-hydroxytryptamine (S-HT)(1A) agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) has been shown to elicit dose-dependent feeding in satiated rats when injected into the midbrain raphe nuclei. Because the feeding-stimulatory effects of this compound are associated with reduced 5-HT release in forebrain, and because recent evidence suggests that medial hypothalamic norepinephrine (NE) and 5-HT may function antagonistically in the control of feeding, the present study sought to determine whether and OH-DPAT would enhance feeding induced by infusing NE into the medial hypothalamus. All experiments were conducted using ad libitum-fed adult male rats with two indwelling cannulas, one aimed at the paraventricular nucleus (PVN), the other at either the dorsal or median raphe. In the first series of experiments rats received a fixed dose of 8-OH-DPAT (0.8 nmol) microinjected into the dorsal or median raphe, as well as NE (0, 10, 20 nmol) administered into the PVN. In the second series, rats received varying doses of raphe 8-OH-DPAT (0, 0.4, 0.8 nmol) coinjected with a single dose of PVN NE (20 nmol). Results indicated that 8-OH-DPAT and NE both elicited reliable increases in 1-h food intake, although their effects did not interact. In the final series, rats were injected with subthreshold doses of both compounds. While combined injections of 8-OH-DPAT and NE modestly increased feeding compared with saline control, this increase was not significantly greater than intake found after injection of 8-OH-DPAT or NE alone. These findings, together with other recent work, fail to support the hypothesis that deficits in brain 5-HT elicited by central administration of 8-OH-DPAT can act to enhance feeding stimulated by medial hypothalamic NE.