REDUCED PARAVENTRICULAR NUCLEUS NOREPINEPHRINE RESPONSIVENESS IN OBESITY-PRONE RATS

Male Sprague-Dawley rats prone to develop diet-induced obesity (DIO-pr one) when fed a high-energy diet have several deficits in brain noradr energic function compared with diet-resistant (DR) rats. To further ch aracterize these deficits, 3-mo-old rats were identified prospectively as being DIO- or DR-prone rats by their high (DIO-prone) or low (DR-p rone) 24-h urine norepinephrine (NE) levels. Saturation-binding studie s with 0.2-20 nM [H-3] paraminoclonidine to aa-adrenoceptors showed 27 -54% decreases in maximal binding capacity in the anterior hypothalami c area, paraventricular nucleus (PVN) and ventromedial hypothalamic nu cleus (VMN), and basolateral amygdalar nucleus of DIO- vs. DR-prone ra ts. The areal extent of the VMN was selectively reduced by 15% in DIO- prone rats. Freely moving, catheterized DIO-prone rats had higher basa l plasma glucose (9%) and insulin (31%) levels. Bilateral 3 nmol NE in fusions over 20 min into the PVN increased plasma NE (175%) and insuli n (31%) levels in DR-prone rats but decreased plasma insulin by 17% an d did not alter plasma NE levels in DIO-prone rats. PVN NE infusions h ad no effect on plasma epinephrine or glucose or motor activity in eit her group. Thus reduced PVN alpha(2)-adrenoceptor binding is associate d with a selective reduction in NE-induced sympathetic activation and insulin release, suggesting a postsynaptic, noradrenergic deficit in D IO-prone rats.