Sustained behavioral stimulation following selective activation of group I metabotropic glutamate receptors in rat striatum.
Group I metabotropic glutamate receptors (mGluRs) are densely expressed in the medium-sized spiny projection neurons of striatum. Activation of this group of the mGluRs modifies neuronal physiology through stimulation of phosphoinositide hydrolysis and intracellular Ca(2)+ release. Unlike the ionotropic glutamate receptors that mediate rapid synaptic transmission, activation of the mGluRs produces long-lasting actions brought about by modulation of activities of intracellular effectors. In this study, the role of the group I mGluRs in the modulation of extrapyramidal motor function was examined using a group I selective agonist, 3, 5-dihydroxyphenylglycine (DHPG), in chronically cannulated rats. Bilateral injections of DHPG at a series of subtoxic doses (20, 40, 80, and 160 nmol) into the central part of the dorsal striatum produced hyperlocomotion and a unique stereotypical behavior (spontaneous and repetitive twitching movement of the head and forepaws) in a dose-dependent manner. The characteristic twitchy behavior usually commenced 30 min to 1 h, and could last as long as 10 to 12 h, after a single injection of the group I agonist. The behavioral responses to DHPG administration were markedly antagonized by intrastriatal injection of the group I antagonist PHCCC (10 nmol), but not the group II/III antagonist MSOPPE (10 nmol). Intrastriatal administration of 20 nmol dantrolene, an inhibitor of intracellular Ca(2)+ mobilization, also prevented DHPG-stimulated motor activities. However, blockade of dopamine D(1) receptors with systemic administration of SCH-23390 (0.1 mg/kg, SC) did not alter the ability of DHPG to provoke behavioral activities. These data indicate that selective activation of the DHPG-sensitive group I mGluRs in the striatum can produce long-lasting stimulation of motor activity. DHPG-induced motor stimulation involves the mobilization of intracellular Ca(2)+ stores, but appears to be independent of D(1) dopaminergic transmission.
Wang
J Q
JQ
Division of Pharmacology, School of Pharmacy, University of Missouri-Kansas City, 2411 Holmes Street, M3-225, Kansas City, MO 64108-2792, USA.
Mao
L
L
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001552:Benzazepines / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D003342:Corpus Striatum / Q000502:physiology*; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D003620:Dantrolene / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*
D001552:Benzazepines; D018094:Receptors, Metabotropic Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D008734:Methoxyhydroxyphenylglycol; D003620:Dantrolene; D002118:Calcium; C010117:3,4-dihydroxyphenylglycol