The role of GABA in the basal ganglia and limbic system for behaviour

Some years ago it was considered that GABA "the major inhibitory transmitter in the CNS" inhibited the activity of the dopamine systems. Today it is evident that the GABA-dopamine interaction is considerably more complex, and in several recent reviews we have discussed that a reevaluation of previous experiments is obviously needed to test whether GABA physiologically may directly inhibit dopamine neuronal activity (43, 45, 49, 50). In this communication will be discussed some of the behavioural functions of GABA studied by the local intracerebral injection technique in rats. We have recently obtained evidence that GABA in the striato-entopeduncular, striato-nigral and the pallido-subthalamic descending GABAergic pathways is mediator of dopamine dependent behaviours related to dopamine receptor stimulation in striatum. The specific GABA agonist muscimol induced strong amphetamine-like stimulation and stereotyped behaviour in the nucleus entopeduncularis (EP) (the medial or inner segment of globus pallidus), the subthalamic nucleus (STN) and the zona reticulata of substantia nigra (SNR) (49, 50). GABA receptor stimulation in EP, STN and SNR mediates according to this new hypothesis the efferent output of striatum (see Fig. 1). This hypothesis may explain the findings that the systemic injection of GABA-facilitating drugs increases the stereotyped licking/gnawing behaviour induced by high doses of dopamine stimulants in rodents (43, 46) and worsens schizophrenic symptoms in the clinic (5, 52).