Profile of NE, DA and 5-HT activity shifts in medial hypothalamus perfused by 2-DG and insulin in the sated or fasted rat

This study was carried out in the unrestrained rat to determine the nature of the in vivo profile of monoamine neurotransmitters within the medial hypothalamus in response to the presence of a glucoprivic or metabolic challenge to neurons within this region. In these experiments, insulin or 2-deoxy-D-glucose (2-DG) was applied locally to the paraventricular nucleus (PVN), dorsomedial nucleus (DMN) and ventromedial hypothalamus (VMH). In each of 11 Sprague-Dawley rats, a guide cannula was implanted stereotaxically to rest just above these structures. Upon recovery, a concentric push-pull cannula system was used to perfuse an artificial CSF within a medial hypothalamic site. The CSF was perfused at a rate of 20 microliters/min with a 5.0 min interval intervening between the collection of each 100 microliters sample. After the rat was fasted for 20-22 hr, either 10 micrograms/microliters 2-DG or 4.0 mU/microliters of insulin was incorporated into the control CSF medium and perfused at the same locus. The aliquots of hypothalamic perfusate were assayed by high performance liquid chromatography with electrochemical detection (HPLC-EC) for the respective concentration in pg/microliter of norepinephrine (NE), dopamine (DA), serotonin (5-HT) and each of their major metabolic products. When the rat was sated, 2-DG enhanced significantly the mean efflux of NE from the medial hypothalamus in comparison to control CSF values. However, under the fasted condition, 2-DG augmented the turnover of both the catecholamine and 5-HT as reflected by elevated levels of MHPG and 5-HIAA, respectively. On the other hand, insulin perfused within the same medial hypothalamic sites evoked a significant increase in the synthesis and release of DA from the sated rat, but did not alter its turnover. Following the interval of fast, insulin produced no immediate alteration in transmitter activity; however, in the interval following insulin's perfusion, DA and 5-HT turnover were enhanced while the efflux of 5-HT was suppressed. An analysis of the proportional values of the levels of the amines to each other revealed marked shifts in the relationships between the catechol- and indoleamine transmitters following local perfusion with both 2-DG and insulin. Overall, NE synthesis and turnover exceeded that of 5-HT following 2-DG, whereas DA predominated over NE and 5-HT during insulin's perfusion.