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 pr ojecting to the motor thalamus is thought to contribute to the pathophysiol ogy of Parkinson's disease. We investigated the functional role of thalamic GABA(B) receptors in a rodent model of Parkinson's disease. First, we exam ined the effects of blockade of GABA(B) receptors in the ventromedial thala mic 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) re ceptor mRNA in the basal ganglia and thalamus using in situ hybridisation. Unilateral microinjections of the GABA(B) receptor antagonist 2-hydroxysacl ofen into the ventromedial thalamic nucleus ipsilateral to the nigrostriata l lesion induced contralateral rotations in a dose-dependent manner. Howeve r, microinjection of antagonists with higher affinity for the GABA(B) recep tor SCH 50911, CGP 56433 and CGP 55845 did not result in rotational behavio ur, but did induce convulsions at higher doses. GABA(B) receptor mRNA expre ssion was found throughout the basal ganglia and thalamus, including the ve ntromedial thalamic nucleus. No statistically significant differences in GA BA(B) mRNA expression were observed in the ventromedial thalamic nucleus fo llowing a unilateral 6-OHDA lesion of the substantia nigra. These results m ake it improbable that thalamocortical GABA(B) receptors play an important role in the pathophysiology of parkinsonism. Therefore, GABA(B) receptors d o not appear to be a promising target for novel antiparkinsonian drugs. (C) 1999 Elsevier Science Ltd. All rights reserved.