Effect of anesthetic doses of γ-hydroxybutyrate on subcortical concentrations of homovanillic acid

Abstract

The naturally occurring central nervous system depressant γ-hydroxybutyrate (GHB) and its lactone precursor γ-butyrolactone (GBL) produce a marked increase in brain dopamine. These agents also appear to cause an effective and quite selective block in the utilization of brain dopamine. Thus administration of GBL, or GHB to rats in anesthetic doses blocks the depletion of dopamine induced by α-methyl-p-tyrosine. Shortly after administration of GBL when brain dopamine levels are rapidly increasing the levels of homovanillic acid remain the same or decrease. As the sleep-inducing effects of the drug wane and the dopamine levels begin to fall, a marked increase in the brain level of homovanillic acid is observed. 1,4-Butanediol, an analogue of γ-hydroxybutyrate, which exerts its central nervous system depression as a result of conversion in vivo to γ-hydroxybutyrate also causes a transient increase in brain dopamine and a fall in homovanillic acid. This effect is followed by a marked increase in homovanillic acid as the dopamine levels fall off to predrug conditions. Anesthetic doses of GBL also antagonize the initial increase in HVA normally produced by the neuroleptic drug, chlorpromazine, either at ambient temperature or at 32°C. Administration of a non-‘sleep’-inducing dose of GBL does not significantly alter the endogenous concentration or markedly interfere with the utilization of subcortical dopamine. A non-‘sleep’-inducing dose of GBL also does not block the chlorpromazine induced increase in homovanillic acid. Administration of other central nervous system depressants, such as chloral hydrate in hypnotic doses does not antagonize the chlorpromazine induced increase in homovanillic acid.