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
GABA(B) receptors in a rodent model of
Parkinson's disease. First, we examined the effects of blockade of
GABA(B) 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
GABA(B) receptor mRNA in the basal ganglia and thalamus using in situ hybridisation. Unilateral microinjections of the
GABA(B) 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
GABA(B) receptor SCH 50911,
CGP 56433 and
CGP 55845 did not result in rotational behaviour, but did induce convulsions at higher doses.
GABA(B) receptor mRNA expression was found throughout the basal ganglia and thalamus, including the ventromedial thalamic nucleus. No statistically significant differences in
GABA(B)
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
GABA(B) receptors play an important role in the pathophysiology of
parkinsonism. Therefore,
GABA(B) receptors do not appear to be a promising target for novel antiparkinsonian drugs.