Dopaminergic and serotoninergic anorectics differentially antagonize insulin- and 2-DG-induced hyperphagia

The efficacy of anorectic drugs has been studied in rats made hyperphagic by injection of insulin or of 2-deoxy-d-glucose (2-DG). It was found that anorectics that act through a serotoninergic mechanism, i.e., d- and d-l-fenfluramine, p-chloroamphetamine, quipazine and fluoxetine antagonize both insulin- and 2-DG-induced overeating, while anorectics acting through the dopaminergic system, i.e., d-amphetamine, diethylpropion, lisuride, bromocriptine and mazindol, antagonize the hyperphagia induced by 2-DG but not that induced by insulin. Neither serotoninergic nor dopaminergic anorectics modified insulin-induced hypoglycaemia. The serotonin (5-HT) receptor blocker metergoline did not modify the hyperphagic response to insulin or 2-DG. The present results indicate that there are different neuronal or humoral circuits underlying the hyperphagic responses to insulin and 2-DG. In addition, these results, which show different effectiveness of anorectic drugs depending on what has provoked the hyperphagia, suggest that differences in the etiology of the hyperphagia of obese subjects must be taken into consideration when choosing therapy.