Effects of fenfluramine on sleep-wakefulness in cats

Abstract

Five cats were prepared with chronically implanted electrodes for recording sleep-wakefulness patterns. Four of these animals received fenfluramine at each of three dose levels and data was recorded for the following 12 hours. Percent of time in paradoxical sleep was significantly reduced by 2.5 and 7.5 mg/kg, but not by 0.5 mg/kg, of fenfluramine. The higher doses also increased slow-wave sleep and, at 7.5 mg/kg (an anorexigenic dose), total sleep time was significantly increased. Under similar conditions amphetamine, at an anorexigenic dose of 1 mg/kg, significantly suppressed both paradoxical sleep and slow-wave sleep in three cats.

Rebound of paradoxical sleep after suppression induced by 2.5 mg/kg of fenfluramine was not seen in either of two cats studied when sleep patterns were recorded for 48 hours. After 7.5 mg/kg of the drug, however, rebound was seen on days 3 and 4 after suppression of paradoxical sleep which lasted for over 26 hours. In two animals, daily administration of 2.5 mg/kg of fenfluramine for 16 consecutive days, followed by saline administration for three days, indicated that tolerance was developing to the suppression of paradoxical sleep produced by the drug.