Be. Levin, REDUCED PARAVENTRICULAR NUCLEUS NOREPINEPHRINE RESPONSIVENESS IN OBESITY-PRONE RATS, American journal of physiology. Regulatory, integrative and comparative physiology, 39(2), 1996, pp. 456-461
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.