In vivo inhibition of veratridine-evoked release of striatal excitatory amino acids by the group II metabotropic glutamate receptor agonist LY354740 in rats

Effects of Single and Repeated Phencyclidine Administration on the Expression of Metabotropic Glutamate Receptor Subtype mRNAs in Rat Brain

“…The alteration of mGluR2 mRNA expression of group II mGluR is consistent with several previous reports that the behavioral and neurochemical changes induced by PCP are related to the group II mGluR , especially mGluR2 (Spooren et al 2000). Recently, several lines of evidence have suggested that the functions of groups II and III mGluR have been presumed to inhibit the modulation of glutamate neural transmission by means of predominantly pre-synaptic mechanisms Battaglia et al 1997;Manzoni et al 1997). Taking into account the above observations, a down-regulation of the level of groups II and III mGluR mRNA may suggest a compensatory decrease, i.e., a disinhibition, to enhance glutamate release during the prolonged reduction of basal glutamatergic transmission after repeated administration of PCP.…”

“…Both the group II and group III mGluRs have been implicated in the modulation of glutamate neural transmission by predominantly presynaptic mechanisms Conn and Pin 1997). As well, selective agonists for groups II and III mGluRs have been shown to decrease the evoked release of glutamate in vitro in synaptosomes (East et al 1995) and brain slices (Di Iorio et al 1996), as well as in vivo microdialysis (Battaglia et al 1997;Cozzi et al 1997), and produce presynaptic inhibitory effects at certain glutamate synapses in electrophysiological studies (Lovinger and McCool 1995;Martin et al 1997). Previously accumulated knowledge of the properties of these receptors in the CNS suggests that they could be candidates for novel drug targets in psychiatric and neurological disorders Moghaddam and Adams 1998).…”

Differential Effects of Antipsychotic and Glutamatergic Agents on the phMRI Response to Phencyclidine

“…This compound is a selective metabotropic glutamate (mGlu) 2/3 receptor agonist that can prevent glutamate hyperexcitation by decreasing the evoked release of glutamate from forebrain and limbic glutamatergic synapses (Schoepp and Marek, 2002;Cartmell and Schoepp, 2000). Consistent with this, LY354740 has been shown to inhibit increases in glutamate induced by the depolarizing agent veratridine in the striatum of freely moving rats (Battaglia et al, 1997), and reduce the response to electrically evoked glutamate release in a manner consistent with a presynaptic site of action (Capogna, 2004;Kilbride et al, 1998). Agonists of mGluR2/3 such as LY354740 can antagonize the behavioral and neurochemical effects of PCP in rodents (Lorrain et al, 2003;Cartmell et al, 1999;Moghaddam and Adams, 1998) and produce a dosedependent suppression of ketamine-induced impairment of working memory by ketamine in human volunteers (Krystal et al, 2005).…”

The Use of Knock-Out Mice Unravels Distinct Roles for mGlu2 and mGlu3 Metabotropic Glutamate Receptors in Mechanisms of Neurodegeneration/Neuroprotection

“…One hypothetical advantage associated with the use of mGlu receptor ligands is the lack of the adverse effects typically induced by NMDA or AMPA receptor antagonists, such as sedation, ataxia, and severe learning impairment Bruno et al, 2001). Of the eight known mGlu receptor subtypes, mGlu2 and mGlu3 receptors are the best candidates as "neuroprotective receptors," because their activation inhibits glutamate release (Lovinger, 1991;Lovinger and McCool, 1995;Battaglia et al, 1997;Cozzi et al, 1997), inhibits voltage-gated calcium channels (for review, see Pin and Duvoisin, 1995), positively modulates potassium channels (Sharon et al, 1997), and stimulates the production of neurotrophic factors in astrocytes and microglia (Bruno et al, 1997(Bruno et al, , 1998bCiccarelli et al, 1999;D'Onofrio et al, 2001;Matarredona et al, 2001). Early in vitro studies have shown that first generation agonists of mGlu2 and mGlu3, such as (2S,1ЈS,2ЈS)-2-(carboxycyclopropyl)glycine and (2S,2ЈR,3ЈR)-2-(2Ј,3Ј-dicarboxycyclopropyl)glycine, are protective against excitotoxicity and other neuronal insults (Pizzi et al, 1993;Bruno et al, 1994Bruno et al, , 1995Ambrosini et al, 1995;Buisson and Choi, 1995;Thomsen et al, 1996).…”