EFFECTS OF SB334867 ON OREXIN-A MEDIATED FOOD AND WATER INTAKE IN THE BED NUCLEUS OF STRIA TERMINALIS

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Orexins are synthesized by lateral hypothalamic neurons which appear to have extensive projections throughout the neuraxis. Orexins have been shown to influence a variety of homeostatic mechanisms such as feeding and drinking behavior. Orexins act on two receptor subtypes, orexin-1 (OX1R) and orexin-2 (OX2R) receptors. Orexin-A (OXA) binds selectively to OX1R, whereas OX2R binds both OXA and orexin-B (OXB). The presence of OX1R in the bed nucleus of stria terminalis (BST) is verified. OXA microinjections into the BST evoked an increase in liquid food intake (FI) and water intake (WI) in a dose dependent manner. Here, the effect of selective OX1R antagonist SB334867 was examined in the BST in male Wistar rats. 0.26 nmol SB334867 was bilaterally microinjected into the BST alone or 15 min before 0.14 nmol OXA microinjections, whether the increases in liquid FI and WI following OXA applications can be antagonized. OXA enhanced liquid food consumption and increased WI as well. SB334867 pretreated OXA groups did not show any significant differences compared to the control groups neither in liquid food, nor in water ingestion. These findings show that the effects of OXA can be antagonized by SB334867 whereas SB334867 alone did not alter intakes indicating that the effects of OXA are mediated by OX1Rs in the BST.This work was supported by National Research Fund of Hungary (C012, M036687), and by the HAS. [J Physiol Sci. 2006;56 Suppl:S210]