Ambient temperature modulation of fenfluramine-induced thermogenesis in the rat

The anti-obesity drug fenfluramine, promotes loss of weight by reducing food intake; however, there is controversy as to whether the drug can also elevate expenditure of energy. Resting consumption of oxygen (VO2) was measured in conscious rats to determine whether the injection of fenfluramine increased metabolic rate and whether prior fasting, or ambient temperature altered the response. Regardless of whether the rats were fed or had been fasted for 22 hr, in a thermoneutral environment (28 degrees C), the intraperitoneal injection of dl-fenfluramine (20 mg/kg) caused a raised oxygen consumption. This elevation was sustained to the end of the 60-min period of measurement after the injection, at which point the colonic temperature was found to be increased. This metabolic response to fenfluramine was largely attenuated when the drug was administered at 23 degrees C, and the colonic temperature of the rats was decreased by 60 min after the injection. At 4 degrees C, the injection of fenfluramine inhibited thermogenesis against cold, the oxygen consumption fell and the rats exhibited hypothermia. It was concluded that fenfluramine can increase the metabolic rate, but that this effect is not conditional on associated food intake, as has been reported. Rather, the ambient temperature governs whether stimulation or inhibition of thermogenesis will be evoked. These metabolic effects of fenfluramine explain, in part, its divergent effects on body temperature, reported previously.