GABA-RECEPTOR ACTIVATION IN THE GLOBUS-PALLIDUS AND ENTOPEDUNCULAR NUCLEUS - OPPOSITE EFFECTS ON REACTION-TIME PERFORMANCE IN THE CAT

The possible role of GABAergic mechanisms in the control of the basal ganglia output structures, the globus pallidus (GP) and the entopedunc ular nucleus (EP), was studied in cats performing a conditioned flexio n movement triggered by an auditory stimulus. The effects of discrete unilateral microinjections of low doses of the GABA(A) receptor agonis t (muscimol 5-100 ng/0.5 mu l) and antagonist (bicuculline methiodide 25-150 ng/0.5 mu l) in the GP and the EP were tested on the motor perf ormance of eight animals trained to release a lever in a simple reacti on time (RT) schedule after an auditory stimulus. Control injections i n neighboring structures did not induce any effect except with five- t o tenfold higher doses in the closest injection sites. The dose of 20 ng muscimol injected into the ventral and medial part of the GP produc ed an arrest of the performance after a few unsuccessful trials (over the RT reinforcement limit of 500 ms), while muscimol injected in site s located in the lateral GP resulted in a dose-dependent lengthening i n RTs, with a concomitant increase in the force change latency. In mos t of the subjects, the force exerted on the lever was higher after mus cimol than after vehicle injection. Force change velocity was then sig nificantly increased. In contrast, muscimol injected in the ventral an d rostral region of the EP produced a decrease in RTs or a complete ce ssation of responding after a high number of anticipatory responses (r elease of the lever before the trigger stimulus). No significant chang es in the force change latency could be observed while there was a non -significant tendency for the force levels to be lowered. Bicuculline injections in the EP were found to increase RTs with a concomitant inc rease in force change latency and a slowness of velocity, while no sig nificant effect was observed following injections in the GP. These res ults suggest that a balance between GABAergic activity in the two outp ut nuclei of the basal ganglia, the GP and the EP, is crucial for the correct initiation and execution of the conditioned motor task.