GABA in the entopeduncular nucleus and the subthalamic nucleus participates in mediating dopaminergic striatal output functions

Abstract

The bilateral intracerebral injection of the specific GABA agonists muscimol (25, 100 ng) and THIP (500 ng) into the pallido-entopeduncular nucleus (EP) and the subthalamic nucleus (STN) of rats induced a behavioural stimulation closely resembling the syndrome evoked by direct stimulation of dopamine receptors in the striatum or by the systemic injection of dopamine agonists. The rats showed strong locomotor and rearing activity followed by characteristic stereotyped behaviour consisting of sniffing and gnawing activity. The stimulation induced by muscimol (25 ng) was found independent of dopamine, since the dopamine antagonist haloperidol (1 mg/kg s.c.) induced no blockade. Injection of the GABA antogonist picrotoxin (100 ng) into the EP or STN induced sedation and catalepsy. The unilateral injection of muscimol and picrotoxin provoked contraversive and ipsiversive postural changes. Related behavioral effects were induced by GABAergic drugs injected in substantia nigra, zona reticulata (SNR). These data provide support for the new hypothesis that GABA in the EP, SNR and STN is important for the expression of behavior related to stimulation of dopamine receptors in the striatum. The effects may be induced by a dopamine activation of the descending striato-EP, striato-SNR GABAergic pathways and possibly also the pallido-STN GABAergic pathway. The findings suggest that in addition to a pathology of the dopamine system there may also be a GABAergic dysfunction in the efferent system of the basal ganglia localized to the EP, SNR and STN in diseases, such as parkinsonism, Huntington's chorea and possibly schizophrenia.