A simple approach to study the effect of haloperidol on GABA functional activity in the nigro-striatal system

The effects of haloperidol on the accumulation of GABA as a function of time in striatum and substantia nigra after administration of an inhibitor of GABA-transaminase (GABA-T), the main catabolizing enzyme of GABA, were studied. In the experiments they have chosen ethanolamine-O-sulphate (EOS), as specific blocker of GABA-T. EOS does not interfere with the other enzymes involved in GABA biosynthesis. Animals receiving EOS plus haloperidol showed a marked sedation compared to those receiving EOS alone. EOS in the dose used produces ptosis and sedation with signs of slight catalepsy. In conclusion, the results reported demonstrate that the GABAergic system indeed participates in the feedback mechanisms modulating the physiological state of dopaminergic neurons. Moreover, a direct connection between GABA neurons and dopamine cell bodies in substantia nigra cannot explain the results of the present study. In fact the increase of GABA accumulation after haloperidol cannot be directly correlated with the increase of dopamine turnover rate in striatum and the increase of firing rate of dopamine cell bodies since GABA is an inhibitory neurotransmitter.