Higher α-noradrenergic receptors in paraventricular nucleus of obese zucker rats: Decline after food deprivation

Norepinephrine (NE), acting through alpha-2-noradrenergic receptors in the hypothalamic paraventricular nucleus (PVN), has been implicated in the control of feeding behavior and body weight gain. To determine whether this hypothalamic receptor system is disturbed in genetically obese rats, the binding of radioligands to alpha-2-noradrenergic, as well as to alpha-1-noradrenergic, receptors was examined in seven hypothalamic nuclei of obese Zucker rats relative to their lean littermates. Receptor binding procedures, using the alpha-2-noradrenergic agonist [H-3]p-aminoclonidine ([H-3]PAC) and the alpha-1-noradrenergic antagonist [H-3]prazosin, demonstrated that the obese rats, compared to the lean rats, had significantly greater alpha-2-noradrenergic and alpha-1-noradrenergic receptor binding, specifically in the PVN as opposed to other hypothalamic areas examined. Moreover, the obese rats, compared to the lean rats, exhibited greater responsiveness to the effects of food deprivation (48 h), which caused a significant decline in radioligand binding to both alpha-2 and alpha-1 receptors, specifically in the PVN. A decrease in alpha-2-receptor binding after deprivation in the obese rats was also seen in two basal hypothalamic areas, namely, the supraoptic nucleus and arcuate nucleus-median eminence. The possibility exists that these disturbances in hypothalamic alpha-receptors may be involved in the development and/or maintenance of the genetic obesity.