Effects of systemic phenylpropanolamine and fenfluramine on serotonin activity within rat paraventricular hypothalamus.
Phenylpropanolamine (PPA) anorexia has been linked to activation of alpha 1-adrenergic receptors within rat paraventricular hypothalamus (PVN) by studies documenting that intra-PVN injection of PPA and other alpha 1-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-HT1a 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.
McMahon
L R
LR
Department of Psychology, Texas A&M University 77843, USA. pjw@psych.tamu.edu
Wellman
P J
PJ
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D005277:Fenfluramine / Q000494:pharmacology*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D017551:Microdialysis; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism*; D010665:Phenylpropanolamine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017661:Receptors, Presynaptic / Q000187:drug effects / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D001067:Appetite Depressants; D017661:Receptors, Presynaptic; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D005277:Fenfluramine; D012701:Serotonin; D010665:Phenylpropanolamine; D006897:Hydroxyindoleacetic Acid; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin