Motor behavior in rats after separate and combined administration of GABAergic agents into the neostriatum

Chronic experiments were performed on rats to study the main inhibitory transmitter system of the neostriatum--the GABAergic system--in the regulation of normal and pathological motor behavior. Studies addressed the effects of separate and combined administration of GABA (45 microg) and A-type receptor antagonists, i.e., picrotoxin (1 microg) and bicuculline (5 microg), into the neostriatum on the performance by rats of spontaneous (including pathological) and conditioned reflex motor behavior (active avoidance reflex in a shuttle box). Agents were injected in a volume of 1 microl daily for three weeks; control animals received physiological saline. Activation of the GABAergic system of the neostriatum had no significant effect on behavior. Conditioned reflex avoidance behavior was impaired throughout the period of bicuculline administration (there was no significant change in spontaneous behavior); this recovered after the course of microinjections finished. Picrotoxin produced smaller negative effects on performance of the reflex, though rats showed clear imperative movements in the form of choreomyoclonic hyperkinesia. Simultaneous administration of picrotoxin and GABA into the neostriatum produced less hyperkinesia; administration of picrotoxin and bicuculline altered the nature of hyperkinesia. The importance of the GABAergic system for the antihyperkinetic activity of the basal ganglia is discussed, and it is suggested that the GABA-A subsystem is of critical importance in these functions.