Effect of gammahydroxybutyric acid on catecholamine synthesis and utilization in the developing rat brain.

Gammahydroxybutyric acid (GHBA) was administered subcutaneously, 750 mg/kg, to 1, 4, 14 and 28 days old rats 30 or 90 min before sacrifice. Whole brain and regional brain levels of tyrosine, dopamine (DA) and noradrenaline (NA) were measured. In some experiments the tyrosine hydroxylase activity was studied by measuring the accumulation of dihydroxyphenylalanine (DOPA) after inhibition of aromatic L-aminoacid decarboxylase. GHBA induced an increase in tyrosine and DA levels at the various ages except at 1 day of postnatal age. The effect of GHBA on the accumulation of DOPA after inhibition of aromatic L-aminoacid decarboxylase varied with age. Thus, tyrosine hydroxylase activity seemed to be enhanced in the 4 days old rats after 90 min and after 30 min in the 28 days old rats. Ninety minutes after GHBA administration to the 28 days old animals, DOPA accumulation reached or was slightly below control levels. Brain NA levels were not affected by GHBA administration. Regional analysis of DA and NA after inhibition of tyrosine hydroxylase with alpha-methyltyrosine demonstrated a reduced disappearance of DA after GHBA in the striatum region already from 4 days of postnatal age. GHBA administration did not affect the nerve impulse release of NA in any of the brain regions studied. It may be concluded that GHBA acts inhibitory on brain DA neurons during early postnatal development.