Effects of systemic phenylpropanolamine and fenfluramine on serotonin activity within rat paraventricular hypothalamus

Phenylpropanolamine (PPA) anorexia has been linked to activation of α1-adrenergic receptors within rat paraventricular hypothalamus (PVN) by studies documenting that intra-PVN injection of PPA and other α1-adrenergic agonists suppress food intake. The present experiments examine the hypothesis that PPA may suppress appetite indirectly via release of serotonin (5-HT) within the PVN. In Experiment 1, we compare the effects of PPA (20 mg/kg, IP, and of d,l-fenfluramine (FEN: 7.5 mg/kg, IP), relative to a vehicle treatment, on extracellular levels of 5-HT and the 5-HT metabolite 5-HIAA in adult male rats prepared with concentric microdialysis probes aimed at either the PVN or the perifornical hypothalamus (PFH). Injection of either vehicle or 20 mg/kg PPA had no significant effect on extracellular 5-HT within the PFH or the PVN. In contrast, a subsequent injection of 7.5 mg/kg FEN produced significant increases in 5-HT and significant decreases in 5-HIAA within the PVN and the PFH. In Experiment 2, the 5-HT(1a), autoreceptor agonist 8-OH-DPAT (0.25 mg/kg, SC) was used to suppress presynaptic release of 5-HT prior to systemic injection of either fenfluramine (5 mg/kg, IP) or PPA (5, 10, 20, and 30 mg/kg, IP). The anorexic action of FEN, but not PPA, was reduced by pretreatment with 8-OH-DPAT. These results suggest that the anorexic action of PPA is not mediated by an indirect effect of PPA on presynaptic release of 5-HT.