Monoamine transmitter activity in lateral hypothalamus during its perfusion with insulin or 2-DG in sated and fasted rat

Abstract

A unique profile of neurochemical events is proposed to occur in the diencephalon which is contingent upon the nutrient status of the animal. In this first of a series of investigations, we selected the lateral hypothalamus (LH) in order to determine its specific resting profile of monoaminergic neurotransmitters and their principal metabolites. The neuronal pattern of activity was studied during sated and fasted conditions as well as during a local glucoprivic challenge to the LH. After permanent guide cannulae for push-pull perfusion were implanted in female Sprague-Dawley rats, the LH was perfused repeatedly with an artificial CSF, at a rate of 20μl/min, in order to collect a series of 5.0 min samples. Aliquots of each perfusate were assayed directly using a high performance liquid chromatography system with electrochemical detection (HPLC-EC) for pg/μl concentrations of norepinephrine (NE), dopamine (DA) and serotonin (5-HT). In comparison to the basal levels of amines during the sated condition, when the rat was food-deprived for 20–22 hr, the release of NE, DA, and 5-HT was significantly lower than that observed under the sated condition. Further, the turnover of NE in the LH was concurrently attenuated as reflected by the lower levels of MHPG in the perfusate, thus demonstrating the modification in catecholamine activity produced in the LH by the condition of hunger. When either 10 μg/μl 2-deoxy-D-glucose (2-DG) or 4.0 mU/μl insulin was incorporated into the CSF perfused in the LH, the efflux of DA was significantly enhanced independent of the state of satiation. In addition, the proportion of both NE and DA to 5-HT was likewise increased by either of these centrally acting substances, while the turnover of 5-HT was enhanced and NE and DA turnovers were reduced. Perfusion of 2-DG in the LH of the fasted rat caused a significant reduction in catecholemine turnover in terms of MHPG/NE, VMA/NE, DOPAC/DA and HVA/DA ratios. Moreover, 2-DG increased NE/5-HT while lowering the NE/DA ratio, and enhanced simultaneously the 5-HTOL/5-HT ratio. In the sated rat, 2-DG attenuated the release of 5-HT from the animal's LH, whereas insulin caused a shift in the proportions of NE/5-HT and DA/5-HT. Further, the peptide served to reduce the efflux of 5-HT, enhanced the turnover of 5-HT while diminishing DA turnover, and shifted the metabolism of NE from MHPG to VMA. Overall, these results demonstrate the extent of the multiple changes which occur simultaneously in the circumscribed release and turnover of 5-HT, NE and DA in the LH of the rat when it is fasted. Each of the locally delivered neuronal challenges exerts an equally distinct effect on the basic pattern of activity of the monoamine neurotransmitters. The functional significance of this neurochemical profile in the hypothalamic mechanisms underlying the control of feeding and hunger is discussed.