Dexfenfluramine and feeding reward

This review describes background experiments and new findings showing that dexfenfluramine inhibits self-stimulation of a lateral hypothalamic (LH) feeding-reward system. Earlier work suggested that self-stimulation excites a pathway to the ventral tegmental area (VTA), where the mesolimbic dopamine system is involved in self-administration of food and drugs. LH stimulation also excites taste neurons in the nucleus tractus solitarius (NTS). This helps explain why stimulation can induce feeding responses and also reward self-stimulation responses. Stimulation-induced feeding and self-stimulation are modulated by physiological signals that control an animal's appetite and body weight. An animal will self-stimulate at a slower rate after it has just eaten, or if it is overweight, or if it is given an anorectic dose of insulin. At the same time, responses to turn off automatic stimulation tend to increase. Paradoxically, racemic fenfluramine decreased both self-stimulation and stimulation-escape, which suggested overall lethargy, but new results show this can be avoided by using just the d isomer. Dexfenfluramine inhibited LH self-stimulation but not stimulation-escape. It also released serotonin in the LH, as shown by microdialysis. These results suggest that dexfenfluramine can release serotonin that has as one of its effects the inhibition of circuitry for feeding-reward.