Identification of the neuronal pathway(s) by which hindbrain-administered ghrelin attenuates angiotensin II-induced fluid intake
Caldwell, Kimberly S.
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The ability of ghrelin to decrease fluid intake is a fairly recent discovery and is not well understood. Previous data from our laboratory indicate that hindbrain-administered ghrelin attenuates angiotensin II (AngII)-induced fluid intake in a manner similar to forebrain-administered ghrelin, and that the paraventricular nucleus of the hypothalamus (PVN) is a key site of convergence of hindbrain sites that respond to ghrelin with forebrain substrates that control AngII-stimulated fluid intake. The neural pathway(s) from ghrelin-responsive structures in the hindbrain to the PVN is unknown, however, as are the specific hindbrain structures involved in mediating the anti-dipsogenic effect of hindbrain-administered ghrelin. The present dissertation experiments sought to answer these open questions by testing the hypotheses that there is a direct neural pathway from the hindbrain to the PVN that is sensitive to ghrelin and that there are specific target sites for the action of hindbrain-administered ghrelin. Aim I addressed the first hypothesis by using immunohistochemistry to identify cells in the hindbrain that are activated by ghrelin and/or project to the PVN. The results of this experiment did not identify a ghrelin responsive pathway that goes directly from the hindbrain to the PVN. This suggests that the neuronal pathway used by hindbrain-administered ghrelin to affect AngII-induced neuronal activity in the PVN is indirect and includes connections with other structures. Aim II addressed the second hypothesis by testing the sufficiency of the nucleus of the solitary tract (NTS) and the lateral parabrachial nucleus (LPBN), likely targets for hindbrain-administered ghrelin, to mediate the anti-dipsogenic effect of ghrelin on AngII-stimulated drinking. Although injections of ghrelin into the NTS did not reduce water or 1.8% NaCl intake stimulated by AngII, ghrelin injected into the lateral portion of the LPBN did reduce licks for 1.8% NaCl, suggesting that the LPBN is sufficient to mediate the effect of ghrelin on AngII-induced saline intake, but not water intake.