Chronic haloperidol administration enhances the gamma-aminobutyric acid level in the rat striatum without altering the glutamate level.

A dose-dependent elevation of striatal gamma-aminobutyric acid (GABA) level was found under chronic treatment with haloperidol, a classical neuroleptic drug. The unaltered GABA level in the substantia nigra is compatible with the existence of GABAergic interneurons in the striatum, which are inhibited by the afferent dopaminergic innervation to the striatum. The glutamate levels of the cerebrospinal fluid (CSF) and different brain regions investigated were not significantly changed by haloperidol. By contrast, we found in an earlier investigation with sulpiride, an atypical neuroleptic drug, a changed glutamate level in the striatum and the CSF and an unaltered GABA level. These findings may correspond to the different clinical effects of classical and atypical neuroleptics.