Effect of γ-hydroxybutyrate on the release of monoamines from the rat striatum

A simple in vitro system was developed to study the effect of gamma-hydroxybutyrate on nerve cell depolarization-induced release of labelled DA and 5-hydroxytryptamine. The release of (3)H-dopamine formed in rat striatal slices incubated with (3)3H-tyrosine was followed. A three minute exposure to K+ (53.0 mM) caused a thirty-fold increase in the release of newly synthesized (3)H-dopamine. This K + -induced release was antagonized when gamma-hydroxybutyrate (1 mM) was present in the medium. Potassium (53.0 mM) increased (eighteen-fold) the release of (3)H-dopamine from striatal slices initially loaded by preincubation with (3)H-dopamine. The K + -induced release of this pool of DA was, however, not antagonized by gamma-hydroxybutyrate.Potassium (53.0 mM) also increased the release from striatal slices of (3)H-5-hydroxytryptamine (5-HT) newly synthesized from (3)H-tryptophan. This K + -induced release of 5-HT was also not inhibited by gamma-hydroxybutyrate. The ability of gamma-hydroxybutyrate to antagonize only the K + -induced release of newly formed DA may explain why this agent causes a rapid and selective increase in brain dopamine.