Effect of haloperidol on glutamate decarboxylase activity in discrete brain areas of the rat.

Using freeze-dried samples of rat brain, the effect of haloperidol on glutamate decarboxylase (GAD) activity without exogenously added pyridoxal-5'-phosphate (PLP) was studied in discrete brain nuclei and areas. Repeated injections of haloperidol produced significant changes in GAD activity in the dorsal part of the caudate nucleus, entopeduncular nucleus, pars reticulata of the substantia nigra, lateral hypothalamic area, and dorsomedial hypothalamic nucleus. A reduction of GAD activity after haloperidol was observed in the entopeduncular nucleus and pars reticulata of the substantia nigra. This finding demonstrates biochemically that haloperidol-induced extrapyramidal behavior may be involved in the reduction of GABAergic transmission in the entopeduncular nucleus and pars reticulata of the substantia nigra. A decrease in GAD activity in the lateral hypothalamic area indicates that interaction between GABAergic neurons as well as dopaminergic neurons may be involved in the haloperidol-induced behavioral changes. In addition, close interaction between GABAergic and dopaminergic systems in the dorsomedial hypothalamic nucleus and dorsal part to the caudate nucleus was demonstrated.