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 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.
de Groote
C
C
Department of Neurology, University of Tübingen, Germany. carmen.de-groote@uni-tuebingen.de
Wüllner
U
U
Löchmann
P A
PA
Luiten
P G
PG
Klockgether
T
T
D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D018756:GABA Antagonists / Q000378:metabolism* / Q000627:therapeutic use; D008297:Male; D016627:Oxidopamine / Q000494:pharmacology; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018080:Receptors, GABA-B / Q000502:physiology*; D013787:Thalamic Nuclei / Q000378:metabolism*
D018663:Adrenergic Agents; D018756:GABA Antagonists; D012333:RNA, Messenger; D018080:Receptors, GABA-B; D016627:Oxidopamine