Sustained behavioral stimulation following selective activation of group Imetabotropic 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 g roup of the mGluRs modifies neuronal physiology through stimulation of phos phoinositide hydrolysis and intracellular Ca2+ release. Unlike the ionotrop ic glutamate receptors that mediate rapid synaptic transmission, activation of the mGluRs produces long-lasting actions brought about by modulation of activities of intracellular effecters. In this study, the role of the grou p I mGluRs in the modulation of extrapyramidal motor function was examined using a group I selective agonist, 3,5-dihydroxyphenylglycine (DHPG), in ch ronically cannulated rats. Bilateral injections of DHPG at a series of subt oxic doses (20, 40, 80, and 160 nmol) into the central part of the dorsal s triatum produced hyperlocomotion and a unique stereotypical behavior (spont aneous and repetitive twitching movement of the head and forepaws) in a dos e-dependent manner. The characteristic twitchy behavior usually commenced 3 0 min to 1 h, and could last as long as 10 to 12 h, after a single injectio n of the group I agonist. The behavioral responses to DHPG administration w ere markedly antagonized by intrastriatal injection of the group I antagoni st PHCCC (10 nmol), but not the group II/III antagonist MSOPPE (10 nmol). I ntrastriatal administration of 20 nmol dantrolene, an inhibitor of intracel lular Ca2+ mobilization, also prevented DHPG-stimulated motor activities. H owever, 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 beha vioral activities. These data indicate that selective activation of the DHP G-sensitive group I mGluRs in the striatum can produce long-lasting stimula tion of motor activity. DHPG-induced motor stimulation involves the mobiliz ation of intracellular Ca2+ stores, but appears to be independent of D-1 do paminergic transmission. (C) 2000 Elsevier Science Inc.