ALTERED ALPHA-1-ADRENOCEPTOR BINDING IN INTACT AND ADRENALECTOMIZED OBESE ZUCKER RATS (FA FA)/

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.