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, su ppresses food intake in rats. However, only limited information is ava ilable as to the effect of intracranial PPA injections on food and wat er intake. In Experiment 1, microinjection of PPA (80-240 nM) into the hypothalamic paraventricular nucleus (PVN) induced a dose-dependent s uppression of feeding (ED50 = 181 nM) but was without significant effe ct 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 pe riod in which extracellular NE within the PVN was monitored via an ind welling microdialysis probe. Systemic injection of PPA suppressed extr acellular NE level within PVN by approximately 70%, an action consiste nt with stimulation by PPA of a presynaptic alpha2-adrenergic autorece ptor. Experiment 3 evaluated whether the alpha2-adrenergic activity of PPA contributes to its feeding-suppressive action. Unlike prior resul ts using the alpha1-antagonist benoxathian, PVN microinjection of the alpha2-antagonist rauwolscine in Experiment 3 of the present study fai led to block systemically induced PPA anorexia. These results further support the contention that PVN alpha1-adrenergic receptors suppress f eeding and suggest that PPA's alpha2-adrenergic effects do not modulat e the anorexic action of PPA.