Effect of gamma-hydroxybutyrate on dopamine and dopamine metabolites in the rat striatum

Gamma-butyrolactone (GBL), a precursor for the naturally occurring central nervous system depressant, gamma-hydroxybutyrate (GHB), administered in anesthetic doses, produces an increase in rat corpus striatum dopamine levels without affecting norepinephrine or serotonin levels. The rise and fall of the dopamine levels coincide with the changes of brain GHB levels and the behavioral effects of the drug. The specific activity of striatal dopamine was found to be greater in rats injected with ³H-tyrosine shortly before or shortly after GBL, as compared with controls, which were not treated with GBL. The specific activity of cortical norepinephrine in GBL-treated rats was not significantly different from that observed in untreated controls. No significant difference was observed in blood or striatal tyrosine specific activity of GBL-treated rats. Levels of dopamine metabolites, dihydroxyphenylacetic acid and homovanillic acid, also increased in the corpus stratium after GBL, but the increase did not occur until after brain levels of GHB began to fall. These results suggest that the drug either increases dopamine synthesis and or blocks the release of dopamine from a rapidly turning over functional compartment within the neurons, or both. Perhaps as a result of the ability of GHB to block the release of dopamine, this drug also interferes with the metabolism of dopamine for a certain period of time after administration.