γ‐Aminobutyric Acid Function in the Rat Striatum Is Under the Double Influence of Nigrostriatal Dopaminergic and Thalamostriatal Inputs: Two Modes of Regulation?

Glutamic acid decarboxylase (GAD), γ‐[ 3 H]‐aminobutyric acid ([ 3 H]GABA) high‐affinity uptake into synaptosomes, and endogenous GABA content were measured in the rat striatum 2–3 weeks following 6‐hydroxydopamine injection in the ipsilateral substantia nigra to destroy the nigrostriatal dopaminergic pathway and after kainic acid injection into the centromedial‐parafascicular complex of the ipsilateral thalamus to lesion the thalamostriatal input. Both lesions resulted in apparent GAD increase concomitant with a decreased [ 3 H]GABA uptake into striatal synaptosomes. GABA content was increased selectively following the dopaminergic lesion. Kinetic analysis of the uptake process for [ 3 H]GABA showed selectively a decreased V max following the dopaminergic lesion; in animals with thalamic lesion, however, the change only concerned the K m , which showed a decreased affinity of the transport sites for [ 3 H]GABA. Determination of K m and V max for GAD action on its substrate glutamic acid showed an increased affinity of GAD for glutamic acid in the case of the dopaminergic lesion without any change in V max , whereas the thalamic lesion resulted in GAD increase concomitant with a selective increase in V max . These data suggest that striatal GABA neurons are under the influence of nigrostriatal dopaminergic neurons which may reduce the GABA turnover, whereas the exact nature of the powerful control also revealed on these neurons following thalamic lesion remains to be determined. Both lesions induced adaptive neurochemical responses of striatal GABA neurons, possibly reflecting in the case of the dopaminergic deprivation an increased GABA turnover.