Release of monoamines from the striatum and hypothalamus: effect of -hydroxybutyrate

Abstract

1. A simple in vitro system was developed to study the effect of gamma-hydroxybutyrate on nerve cell depolarization-induced release of labelled dopamine, noradrenaline and 5-hydroxytryptamine from brain slices.2. The release of (3)H-dopamine formed in rat striatal slices incubated with (3)H-tyrosine was followed either by transferring the slices through successive media or by using a superfusion system. A one to three minute exposure to K(+) (53 mM) caused up to a thirty fold increase in the release of newly synthesized (3)H-dopamine. This K(+)-induced release was antagonized when gamma-hydroxybutyrate (1 x 10(-3)M) was present in the medium.3. Potassium (53 mM) increased (eighteen to thirty fold) the release of (3)H-dopamine from striatal slices initially loaded by preincubation with (3)H-dopamine. However, the K(+)-induced release of this pool of dopamine was not antagonized by gamma-hydroxybutyrate.4. Potassium (53 mM) also increased the release from striatal slices of (3)H-5-hydroxytryptamine newly synthesized from (3)H-tryptophan. This K(+)-induced release of 5-hydroxytryptamine was also not inhibited by gamma-hydroxybutyrate.5. The release of newly synthesized (3)H-noradrenaline from hypothalamic slices was also increased by K(+). This K(+)-induced release, however, unlike that of 5-hydroxytryptamine, was antagonized when gamma-hydroxybutyrate was present in the superfusion medium.6. Removal of Ca(++) had no effect on K(+)-induced release of (3)H-dopamine when followed by transferring the slices through successive media. This K(+)-induced release was abolished, however, when Mg(++) (12 mM) was present in the medium.7. The removal of Ca(++) from the superfusion medium abolished almost completely the K(+)-induced release from striatal slices of either newly synthesized (3)H-dopamine or preloaded (3)H-dopamine. This is presumably due to a more effective washout of tissue Ca(++) by the superfusion technique.8. The ability of gamma-hydroxybutyrate to antagonize the K(+)-induced release of monoamines from brain slices does not appear to be unique to the release of newly synthesized dopamine from the striatum.