Neurotensin releases norepinephrine differentially from perfused hypothalamus of sated and fasted rat

The central injection of neurotensin (NT) has been reported to attenuate the intake of food in the fasted animal. To determine whether endogenous norepinephrine (NE) is involved in the satiating effect of NT, the in vivo activity of NE in circumscribed sites in the hypothalamus of the unanesthetized rat was examined. Bilateral guide tubes for push-pull perfusion were implanted stereotaxically to rest permanently above one of several intended sites of perfusion, which included the paraventricular nucleus (PVN), ventromedial nucleus (VMN), and the lateral hypothalamic (LH) area. After endogenous stores of NE at a specific hypothalamic locus were radiolabeled by microinjection of 0.02-0.5 mu Ci of [3H]NE, an artificial cerebrospinal fluid was perfused at the site at a rate of 20 microliter/min over successive intervals of 5.0 min. When 0.05 or 0.1 micrograms/microliter NT (0.03-0.6 mM) was added to the perfusate, the peptide served either to enhance or reduce the local release of NE at 50% of the sites of perfusion. In these experiments, the circumscribed effect of NT on the characteristics of catecholamine efflux depended entirely on the state of hunger or satiety of the rat. That is, when NT was perfused in the fully satiated rat, NE release was augmented within the PVN or VMN; conversely, NE release was inhibited in the LH. In the animal fasted for 18-22 h, NT exerted an opposite effect on the activity of NE within the same anatomical loci in that the efflux of NE was enhanced in the LH but attenuated or unaffected in the PVN or VMN.(ABSTRACT TRUNCATED AT 250 WORDS)