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  4. The ablation of hindbrain catecholamine neurons innervating medial hypothalamic nuclei abolishes glucoprivic feeding, but spares the orexigenic response to ghrelin

The ablation of hindbrain catecholamine neurons innervating medial hypothalamic nuclei abolishes glucoprivic feeding, but spares the orexigenic response to ghrelin

Emanuel AJ, Dinh TT, Ritter S (2008) The ablation of hindbrain catecholamine neurons innervating medial hypothalamic nuclei abolishes glucoprivic feeding, but spares the orexigenic response to ghrelin. Neuroscience 2008 Abstracts 85.2/RR15. Society for Neuroscience, Washington, DC.

Summary: Ghrelin is an orexigenic peptide synthesized in the stomach and secreted during fasting. Receptors for ghrelin are present in the brain and direct injection of ghrelin into the brain evokes feeding. Nevertheless, Y. Date et. al. (2002) have claimed that gastric vagal afferent neurons are the major pathway conveying ghrelin’s signals for starvation and growth hormone secretion to the brain. Furthermore, this group (Date et. al., 2006), has reported that noradrenergic neurons transmit ghrelin’s orexigenic signals from the hindbrain to the hypothalamus. The latter assertion was based on the loss of ghrelin-induced feeding in rats injected into the arcuate nucleus (ARC) with anti-dopamine beta hydroxylase (DBH) conjugated to saporin (DSAP), which retrogradely destroys DBH-containing neurons. We previously showed that DSAP microinjection either into the hypothalamic paraventricular nucleus (PVH) or ARC abolished glucoprivic feeding. Since glucoregulatory responses include alterations of both feeding and growth hormone secretion, we reasoned that the same catecholamine neurons sensitive to glucoprivation may contribute to these responses following ghrelin. To investigate this issue further, we microinjected DSAP (n=7) or unconjugated saporin (SAP control, n=7) bilaterally into the PVH of Sprague-Dawley rats (approximately 400 g BW). Three weeks later, daytime tests for feeding responses to 2-deoxyglucose (2DG, 200 mg/kg, 4-hr test) and ghrelin (15 µg/kg, i.p., 2-hr test) were conducted. As expected, DSAP abolished 2DG-induced feeding. However, the response to ghrelin was not abolished in DSAP treated rats. In fact, feeding in response to ghrelin was significantly enhanced in DSAP-treated rats, compared to the control SAP group (p<0.05). These results confirm our prior findings relative to the role of catecholamine projections in glucoprivic responses, but they contradict the results previously reported by Date et. al. The difference between our injection sites (we injected DSAP into the PVH, and Date injected into the ARC) is not likely to account for the different results since injections of DSAP into either site eliminate DBH terminals throughout the medial hypothalamus and appear to lesion the same population of catecholamine neurons. Therefore, until more detailed analysis is conducted, we conclude that hindbrain catecholamine neurons are required for glucoprivic but not ghrelin-induced feeding.

Related Products: Anti-DBH-SAP (Cat. #IT-03)

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