Activation of striatal group II metabotropic glutamate receptors has a differential effect on dopamine-D1 and -D2 receptor antagonist-induced hypokinesia in the rat.
Motor function of group II metabotropic glutamate receptors was investigated by quantifying motor effects of bilateral infusions of the preferential group II metabotropic glutamate receptor agonist (2S,3S,4S)-alpha-carboxycyclopropyl-glycine (15, 30, 60 nmol/0.5 microl) into the striatum of conscious rats. (2S,3S,4S)-alpha-carboxycyclopropyl-glycine reduced spontaneous sniffing activity in an experimental chamber, but did not affect spontaneous locomotor (line crossings) or exploratory behaviour (rearings, hole visits) in an open field equipped with a hole-board. Intrastriatal infusion of the selective group III metabotropic glutamate receptor agonist L-2-amino-4-phosphobutyric acid (15, 30, 60, 120 nmol/0.5 microl) did not influence spontaneous motor behaviour. Intrastriatal infusion of (2S,3S,4S)-alpha-carboxycyclopropyl-glycine (15 nmol/0.5 microl and 30 nmol/0.5 microl) further depressed spontaneous motor behaviour in rats pretreated with the dopamine-D1 receptor antagonist (-)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5H- benzo[d]naphtho-(2,1-b)azepine, but not if rats were pretreated with the preferential dopamine-D2 receptor antagonist haloperidol. It appears likely that the depression of spontaneous motor behaviour evoked by the preferential group II agonist (2S,3S,4S)-alpha-carboxycyclopropyl-glycine is mediated by activation of group II metabotropic glutamate receptors, since activation of group I metabotropic glutamate receptors has been shown to stimulate motor behaviour, and activation of group III metabotropic glutamate receptors had no effect, as shown in this study. Therefore, it is reasonable to speculate that the striatum may contribute to the motor-depressant effects of systemically applied group II metabotropic glutamate receptor agonists, as reported by us recently. The present findings further suggest that a functional dopamine-D1 antagonism contributes to the motor effects of group II metabotropic glutamate receptor agonists.
Kronthaler
U O
UO
Scantox A/S, Lille Skensved, Denmark. uk@scantox.dk
Schmidt
W J
WJ
D000600:Amino Acids, Dicarboxylic / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001552:Benzazepines / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors*; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists* / Q000502:physiology
C114785:2-amino-4-phosphono-propinate; D000600:Amino Acids, Dicarboxylic; D001552:Benzazepines; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D018690:Excitatory Amino Acid Agonists; D011422:Propionates; D017447:Receptors, Dopamine D1; D018094:Receptors, Metabotropic Glutamate; C058081:ecopipam; C035261:(alpha-carboxycyclopropyl)glycine; D006220:Haloperidol