Functional characterization and expression of thalamic GABA(B) receptors in a rodent model of Parkinson's disease

Increased GABAergic neurotransmission of the basal ganglia output nuclei projecting to the motor thalamus is thought to contribute to the pathophysiology of Parkinson’s disease. We investigated the functional role of thalamic GABAB receptors in a rodent model of Parkinson’s disease. First, we examined the effects of blockade of GABAB receptors in the ventromedial thalamic nucleus of rats with a unilateral 6-OHDA lesion of the substantia nigra on locomotor activity. In addition we studied the expression of GABAB receptor mRNA in the basal ganglia and thalamus using in situ hybridisation. Unilateral microinjections of the GABAB receptor antagonist 2-hydroxysaclofen into the ventromedial thalamic nucleus ipsilateral to the nigrostriatal lesion induced contralateral rotations in a dose-dependent manner. However, microinjection of antagonists with higher affinity for the GABAB receptor SCH 50911, CGP 56433 and CGP 55845 did not result in rotational behaviour, but did induce convulsions at higher doses. GABAB receptor mRNA expression was found throughout the basal ganglia and thalamus, including the ventromedial thalamic nucleus. No statistically significant differences in GABAB mRNA expression were observed in the ventromedial thalamic nucleus following a unilateral 6-OHDA lesion of the substantia nigra. These results make it improbable that thalamocortical GABAB receptors play an important role in the pathophysiology of parkinsonism. Therefore, GABAB receptors do not appear to be a promising target for novel antiparkinsonian drugs.