Effects of blockade of metabotropic glutamate receptors in the subthalamic nucleus on haloperidol-induced Parkinsonism in rats.
The present study examined the postural effects of unilaterally local injection of metabotropic glutamate receptor (mGluR) antagonists into the subthalamic nucleus (STN), in rats with haloperidol-induced parkinsonism. In rats which received unilateral microinjections of (+)-alpha-methyl-4-carboxyphenylglycine (MCPG), a selective, subtype-non-specific antagonist of mGluR, but not the vehicle, into the STN, systemic administration of haloperidol induced ipsiversive dystonic posturing. The severity of the dystonic posturing was dose-dependent. However, subtype-specific antagonists of group I, II, or III mGluRs induced no dystonic posturing. The present findings suggest that the activity of the STN under conditions of dopamine blockade is facilitated by blockade of mGluRs in the STN, suggesting that mGluRs exert inhibitory influence on glutamate release in the STN.
Miwa
H
H
Department of Neurology, Tokyo Metropolitan Institute for Neuroscience, 2-6 Musashidai, Fuchu-city, Tokyo, Japan.
Nishi
K
K
Fuwa
T
T
Mizuno
Y
Y
D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D018492:Dopamine Antagonists; D004421:Dystonia / Q000503:physiopathology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006220:Haloperidol; D008297:Male; D008845:Microinjections; D010302:Parkinson Disease, Secondary / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D011187:Posture; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020531:Subthalamic Nucleus / Q000187:drug effects* / Q000378:metabolism
D001565:Benzoates; D018492:Dopamine Antagonists; D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; C079694:alpha-methyl-4-carboxyphenylglycine; D006220:Haloperidol; D005998:Glycine