Be. Levin et al., ALTERED ALPHA-1-ADRENOCEPTOR BINDING IN INTACT AND ADRENALECTOMIZED OBESE ZUCKER RATS (FA FA)/, Brain research, 614(1-2), 1993, pp. 146-154
While many autonomic and metabolic defects associated with genetic obe
sity in the Zucker rat are corrected by adrenalectomy (Adx), brain adr
enoceptor function has not been examined in this context. Here, 3 week
s after Adx or sham surgery, brains of 11 weeks old lean (Fa / Fa) and
obese (fa / fa) male Zucker rats were assayed for alpha1-([H-3]prazos
in; [H-3]PRZ) and alpha2-adrenoceptor ([H-3]paraminoclonidine; [H-3]PA
C) binding by autoradiography. By genotype, obese Tats had 19-256% hig
her [H-3]PRZ binding than lean rats in the amygdala (central [ACN], ba
solateral [ABL], basomedial [ABM] and medial [MAN] nuclei [n.]), hypot
halamus (dorsomedial n. [DMN] and lateral [LH]) and somatosensory cort
ex. In the ABL and ACN, increased maximal binding (B(max)) in obese ra
ts was associated with decreased affinity (increased K(d)). Three week
s after surgery, sham-operated obese rats gained 27% more weight than
lean rats but lean and obese Adx rats gained the same amount of weight
. Adx reduced [H-3]PRZ binding in both lean and obese rats by 37-70% i
n the amygdala (ABM, ACN, MAN) compared to sham-operated rats. But, Ad
x selectively reduced [H-3]PRZ binding only in lean rats in the ABL, D
MN, ventromedial hypothalamic n. (VMN) and ventroposteromedial thalami
c n. In most areas, decreases in maximal binding (B(max)) associated w
ith Adx were accompanied by decreases in K(d). Unlike [H-3]PRZ binding
, there was no consistent genotype difference in [H-3]PAC binding alth
ough Adx was followed by increased binding in obese and decreased bind
ing in lean rats in the ABL. In only the VMN, obese rats had a 21% hig
her alpha2- to al-adrenoceptor ratio than lean rats. While widespread
differences in brain alpha1-adrenoceptor binding between lean and obes
e rats may be important, the selectively higher VMN alpha2-/alpha1-rat
io may be critical to the pathogenesis of obesity.