Induction of NADH-dependent aldehyde reductase by successive administration of barbiturates in rat brain

The effect of long-term administration of phenobarbital (PB) or barbital for five weeks on brain aldehyde reductase (A1R) and aldehyde dehydrogenase (A1DH) activities in the rat was studied. Mitochondrial (m)-A1DH and NADH-dependent A1R activities were significantly increased over control values after five-week treatment with PB or barbital, while no significant alteration of supernatant (s)-A1DH and NADPH-dependent A1R activities was observed under the same condition. Increase in m-A1DH activity by the treatment with barbiturates was recovered to the control level, however, increased activity of NADH-dependent A1R was maintained even after the cessation of the treatment. In groups of rats pretreated with barbiturates for five weeks, no animals were induced to sleep after intracerebroventricular injection of PB, and this finding strongly suggests the decrease in sensitivity of rats to barbiturates.