Reduced paraventricular nucleus norepinephrine responsiveness in
obesity-prone rats.
Levin, Barry E.
Neurology Service, Department of Veterans Affairs Medical Center,
East Orange 07108; and Department of Neurosciences, New Jersey,
Medical School, Newark, New Jersey 07103
APStracts 2:0276R, 1995.
Male Sprague-Dawley rats prone to develop diet-induced obesity (DIO
-prone) when fed a high energy diet have several deficits in brain
noradrenergic function as compared to diet resistant (DR) rats. To
further characterize these deficits, 3mo old rats were identified
prospectively as being DIO- or DR-prone rats by their high (DIO-) and
low (DR-prone) 24 h urine norepinephrine (NE) levels, respectively.
Saturation binding studies with 0.2-20 nM 3H paraminoclonidine to
[alpha]2-adrenoceptors showed 27-54% decreases in Bmax in the
anterior hypothalamic area, paraventricular n. (PVN) and ventromedial
n. (VMN) and basolateral amygdalar n. of DIO- vs. DR-prone rats. The
areal extent of the VMN was selectively reduced by 15% in DIO-prone
rats. Freely moving, catheterized DIO-prone rats had higher basal
plasma glucose (9%) and insulin (31%) levels. Bilateral 3 nmol NE
infusions over 20 min into the PVN increased plasma NE (175%) and
insulin (31%) levels in DR-prone rats but decreased plasma insulin by
17% and did not alter plasma NE levels in DIO-prone rats. PVN NE
infusions had no effect on plasma epinephrine or glucose or motor
activity in either group. Thus, reduced PVN [alpha]2-adrenoceptor
binding is associated with a selective reduction in NE-induced
sympathetic activation and insulin release suggesting a postsynaptic,
noradrenergic deficit in DIO-prone rats.
Received 5 July 1995; accepted in final form 19 September 1995.
APS Manuscript Number R416-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 14 November 95