Changes in serotonin turnover and the brain sensitivity to barbiturates by disulfiram treatment in rats

The influence of intraperitoneal administration of disulfiram on the serotonin (5HT) turnover and the brain sensitivity to barbiturates were investigated in rats. Treatment of the animals with 200 mg/kg disulfiram resulted in the prolongation of duration of barbiturate-induced hypnosis. This indication and increment of the brain sensitivity to barbiturates after disulfiram treatment. Under the identical condition, disulfiram caused both the reduction of turnover of 5HT and the elevation of 5HT levels, although this effect was less potent than that of phenobarbital. Furthermore, simultaneous administration of disulfiram and phenobarbital resulted in the severe retardation of 5HT metabolism. These results strongly suggest that disulfiram potentiates the hypnotic action of barbiturates by altering 5HT metabolism in rat brain.