Adrenalectomy enhances the anorectic effect of dexfenfluramine: relation to mineralocorticoids and salt appetite.
A previous observation that adrenalectomized (ADX) rats were more anorectic and lost more weight than intact controls when treated with the serotonergic agent, d,l-fenfluramine, was confirmed using a high dose of the more selective d-enantiomer, dexfenfluramine (DFEN). However, ADX rats were not more anorectic than intact controls to a lower dose of DFEN. The extreme weight loss at high doses was accompanied by a loss of appetite for NaCl solution. The rapid deterioration of these animals may have been due to excessive loss of sodium ions and extracellular fluid volume, although this was not assessed directly. This interpretation was supported in a second study in which treatment of ADX rats with a selective mineralocorticoid, which eliminates both the need and appetite for NaCl, normalized weight loss during DFEN treatment. These data do not support the idea of an interactive role of glucocorticoids and brain serotonin in anorexia. The density of serotonin uptake sites in frontal cortex was reduced by DFEN in a dose-dependent manner, but did not differ between ADX and intact control groups.
Department of Psychology, University of Florida, Gainesville 32611.
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Rowland
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LM
Dotson
D000311:Adrenal Glands / Q000187:drug effects* / Q000502:physiology; D000315:Adrenalectomy; D000818:Animals; D001066:Appetite / Q000187:drug effects* / Q000502:physiology; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D003900:Desoxycorticosterone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005277:Fenfluramine / Q000494:pharmacology*; D005625:Frontal Lobe / Q000187:drug effects / Q000502:physiology; D006815:Hunger / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008901:Mineralocorticoids / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000502:physiology*; D014882:Water-Electrolyte Balance / Q000187:drug effects / Q000502:physiology
D008901:Mineralocorticoids; D005277:Fenfluramine; D012701:Serotonin; D003900:Desoxycorticosterone