Protection against acute amphetamine-induced behavior by microinjection of a group II metabotropic glutamate receptor agonist into the dorsal striatum of rats.
Group II metabotropic glutamate receptors (mGluRs) are distributed both pre- and postsynaptically in the striatum. By bilaterally administering a subgroup-selective agonist or antagonist into the dorsal striatum of chronically cannulated rats, this study examined the role of striatal group II mGluRs in the regulation of basal and dopamine-stimulated motor behavior. Intrastriatal injection of a group II agonist, (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV, 0.01, 0.1 and 1 nmol), dose-dependently reduced basal levels of motor activity. Pretreatment of rats with intrastriatal DCG-IV at a higher dose (1 nmol), but not a lower dose (0.01 nmol), produced complete or partial blockade of hyperlocomotion induced by acute injection of amphetamine (2.5 mg/kg, i.p.) or apomorphine (1 mg/kg, s.c.), respectively. Blockade of group II mGluRs by intrastriatal injection of a group II antagonist, (RS)-alpha-methylserine-O-phosphate monophenyl ester (10 nmol), was found to: (i) induce a moderate locomotion by itself; (ii) augment amphetamine-stimulated behaviors and (iii) attenuate DCG-IV-induced reduction of basal and amphetamine-stimulated motor activity. These data demonstrate that the group II mGluRs in the striatum play a significant role in the inhibitory modulation of tonic and phasic motor activity, which is most likely processed through both pre- and postsynaptic mechanisms.
Mao
L
L
Division of Pharmacology, School of Pharmacy, University of Missouri-Kansas City, 64108-2792, USA.
Wang
J Q
JQ
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D003342:Corpus Striatum / Q000502:physiology*; D003521:Cyclopropanes / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005998:Glycine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists* / Q000037:antagonists & inhibitors; D013997:Time Factors
D003521:Cyclopropanes; D015259:Dopamine Agents; D018491:Dopamine Agonists; D018094:Receptors, Metabotropic Glutamate; C082313:2-(2,3-dicarboxycyclopropyl)glycine; D000661:Amphetamine; D001058:Apomorphine; D005998:Glycine