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Reversal of phenylpropanolamine anorexia in rats by the alpha-1 receptor antagonist benoxathian

https://doi.org/10.1016/0091-3057(91)90261-YGet rights and content

Abstract

Phenylpropanolamine (PPA) is a phenethylamine anorectic drug that exerts direct agonist effects predominantly on alpha-1 adrenergic receptors, with some alpha-2 adrenergic activity. Direct injections of PPA as well as the alpha-1 agonist 1-phenylephrine into rat paraventricular nucleus (PVN) suppress feeding. In the present study, we evaluate the hypothesis that systemic PPA acts within the PVN on an alpha-1 receptor population to suppress feeding. Accordingly, adult male rats were prepared with a unilateral guide cannula aimed at the PVN. Microinjection of the alpha-1 adrenergic receptor antagonist benoxathian (0, 2.5, 5.0 or 10.0 nmol) into the PVN was found to have no effect on baseline feeding behavior. Microinjection of 10.0 nmol benoxathian into the PVN completely reversed the anorexia induced by 2.5, 5.0 or 10.0 mg/kg PPA (IP), yet did not alter the hypodipsia produced by PPA. These data strongly suggest that PPA anorexia is mediated by an alpha-1 adrenergic satiety mechanism within the PVN.

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    Consistent with the opposing roles of α1 and α2 adrenoceptors within the noradrenergic system, these subtypes exert opposing actions on feeding and body weight. Thus, pharmacological studies suggest that α1AR agonists may reduce feeding (Morien et al., 1993), at least in part by activation of receptors located in the hypothalamus (Wellman and Davies, 1991, 1992). By contrast, activation of α2ARs particularly by infusion into the paraventricular nucleus of the hypothalamus increases feeding by increasing meal size but leaves meal frequency unaffected (Shor-Posner et al., 1998).

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