Abstract
Barbiturates increased the concentration of brain 5-hydroxytryptamine (5-HT) in rats, when administered in the doses that produced sleep and hypothermia. The increase of 5-HT followed by the increase of 5-hydroxyindoleacetic acid (5-HIAA) in the brain. Brain 5-HT increased immediately after the administration of thiopental sodium and pentobarbital sodium, and the righting reflex disappeared, simultaneously. With phenobarbital sodium, the significant increase in brain 5-HT and the loss of righting reflex were observed 30 minutes after the administration. With barbital sodium, the significant increase in brain 5-HT occurred 30 minutes after the administration, and the righting reflex disappeared 60 minutes after the administration.
In each of the barbiturates used, the time course of hypothermia induced by barbiturate was similar to that of the 5-HT increase in brain by the drug.
The brain 5-HT level was higher in cases treated with reserpine and pentobarbital sodium successively than in those with reserpine alone. Brain 5-HIAA was, also, markedly increased in reserpinized rats and more increased with the combined administration of pentobarbital sodium and reserpine.
Barbiturates did not inhibit monoamine oxidase activity both in vivo and in vitro. The increase of brain 5-HT concentration is supposed not due to the inhibition of monoamine oxidase activity but depends on the activation of 5-HT synthesis.
The 5-HIAA level was higher in rats treated with thiopental sodium and probenecid than in those with probenecid alone. It suggests that the increase in brain 5-HIAA does not depend on the inhibition of the active transport of 5-HIAA but depends on the increase of 5-HT turnover by barbiturates.
These results suggest that the increase of brain 5-HT and its utilization play an important role in the loss of righting reflex and hypothermia induced by the barbiturates used.
