Motor stimulation following bilateral injection of the group-I metabotropic glutamate receptor agonist into the dorsal striatum of rats: evidence against dependence on ionotropic glutamate receptors.
BACKGROUND
Group-I metabotropic glutamate receptors (mGluRs) are densely expressed in the medium-sized spiny projection neurons of the striatum. Activation of the group-I mGluRs in the rat striatum with a selective group-I agonist, 3,5-dihydroxyphenylglycine (DHPG), produced locomotion and stereotypical behavior.


OBJECTIVE
This study was designed to evaluate dependence of DHPG-stimulated motor behaviors on the ionotropic glutamate receptors [N-methyl-D-aspartate (NMDA) and kainate/alpha-amino-3-hydroxy-5-methyl-4-isoxazoleprionic acid (AMPA)].


METHODS
In chronically cannulated rats, effects on motor activity of DHPG injected into the dorsal striatum were examined in the presence or absence of the antagonists selective for NMDA or kainate/AMPA receptors.


RESULTS
Bilateral injections of DHPG (80 nmol) into the dorsal striatum induced a delayed locomotion followed by a prolonged stereotypical behavior characterized by the repetitive twitching movement of the head and forepaws. Blockade of NMDA receptors with intrastriatal injection of the NMDA receptor antagonist, (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP, 2.5 nmol), did not attenuate the behavioral changes induced by DHPG administration. Conversely, CPP unmasked an early onset of locomotion in response to DHPG injection as opposed to the delayed locomotion induced by DHPG in the absence of CPP. Pretreatment of rats with the kainate/AMPA receptor antagonist, 6,7-dinitroquinoxaline2,3-dione (DNQX, 10 nmol), had no effect on DHPG-stimulated behaviors. CPP administered alone sedated animals, whereas DNQX given alone did not alter spontaneous behavioral activity.


CONCLUSIONS
Motor stimulation induced by activation of the DHPG-sensitive group-I mGluRs in the striatum is independent upon co-activation of NMDA or kainate/AMPA receptors, since the NMDA or the kainate/AMPA receptor antagonist had no effect on DHPG-stimulated motor activity.
Mao
L
L
Division of Pharmacology, School of Pharmacy, University of Missouri-Kansas City, 64108-2792, USA.
Wang
J Q
JQ
D000818:Animals; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007608:Kainic Acid / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects*; D016202:N-Methylaspartate / Q000008:administration & dosage / Q000494:pharmacology; D017072:Neostriatum / Q000166:cytology / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology; D011810:Quinoxalines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000187:drug effects*; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012118:Resorcinols / Q000494:pharmacology*; D013268:Stimulation, Chemical
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D010879:Piperazines; D011810:Quinoxalines; D017470:Receptors, Glutamate; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D012118:Resorcinols; C104077:metabotropic glutamate receptor type 1; C079215:3,5-dihydroxyphenylglycine; C056723:FG 9041; D016202:N-Methylaspartate; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D007608:Kainic Acid; D005998:Glycine