Effects of intraventricular gamma-acetylenic-GABA on GABA concentrations, GABA-T and GAD in several areas of the chick brain.

The great interest in new compounds able to increase GABA concentration in the brain as potential antiepileptic drugs has led to the synthesis of powerful inhibitors of GABA transaminase (GABA-T) e.g. gamma-acetylenic GABA (GAG) and gamma-vinyl-GABA. Present experiments were aimed to study behavioral, electrocortical and biochemical effects of GAG after its intraventricular injection. It has been shown that in chicks the microinjection of GAG into the third cerebral ventricle produced a biphasic behavioral and electrocortical syndrome : an initial phase of behavioral and electrocortical sleep followed by a paradoxycal increase in motor activity and a very intense behavioral and ECoG arousal pattern. In addition intraventricular GAG (0.8 mumol) produced a significant increase 1 and 2 h later in GABA concentration in the diencephalon and brain-stem whereas no changes occurred in other brain areas e.g. cerebral hemispheres, optic lobes. Higher doses (1.6 mumol), produced after 1 h, concomitantly to the increased GABA concentration, a significant GABA-T inhibition and a profound inhibition of glutamate-decarboxylase in the diencephalon and brain-stem. Present experiments may explain the paradoxical behavioral, motor and electrocortical stimulation observed at the time of GABA increase concentration and suggest that a small functional neuronal pool of GABA, more than the whole absolute levels of GABA in a given area of the brain, seems to be involved in the control of GABAergic mediated inhibitory mechanisms.