AN ASSESSMENT OF THE INVOLVEMENT OF PARAVENTRICULAR HYPOTHALAMIC ALPHA-2-ADRENOCEPTORS IN PHENYLPROPANOLAMINE ANOREXIA

Systemic injection of phenylpropanolamine (PPA), an alpha1-adrenergic receptor agonist with some activity at alpha2-adrenergic receptors, suppresses food intake in rats. However, only limited information is available as to the effect of intracranial PPA injections on food and water intake. In Experiment 1, microinjection of PPA (80-240 nM) into the hypothalamic paraventricular nucleus (PVN) induced a dose-dependent suppression of feeding (ED50 = 181 nM) but was without significant effect on water intake. Experiment 2 evaluated the effect of systemic PPA on paraventricular hypothalamic norepinephrine (NE) levels. Rats were treated with either vehicle or 20 mg/kg (IP) PPA prior to a 100-min period in which extracellular NE within the PVN was monitored via an indwelling microdialysis probe. Systemic injection of PPA suppressed extracellular NE level within PVN by approximately 70%, an action consistent with stimulation by PPA of a presynaptic alpha2-adrenergic autoreceptor. Experiment 3 evaluated whether the alpha2-adrenergic activity of PPA contributes to its feeding-suppressive action. Unlike prior results using the alpha1-antagonist benoxathian, PVN microinjection of the alpha2-antagonist rauwolscine in Experiment 3 of the present study failed to block systemically induced PPA anorexia. These results further support the contention that PVN alpha1-adrenergic receptors suppress feeding and suggest that PPA's alpha2-adrenergic effects do not modulate the anorexic action of PPA.