Table 2.
Summary of Preclinical Studies Supporting a Role of mGluRs in Schizophrenia
| Receptor Subtype | Pharmacological Tool | Effect | References |
|---|---|---|---|
| Group I | |||
| mGluR1 | EMQMCM (antagonist) | ↔ MK-801-induced locomotor hyperactivity in rats; | Pietraszek et al. 2005 |
| ↔ MK-801-induced deficits in prepulse inhibition in rats | |||
| mGluR5 | MPEP (antagonist) | ↔ MK-801-induced locomotor hyperactivity in rats; ↑ MK-801-induced impairments of spatial working memory and instrumental learning in rats | Homayoun et al. 2004 |
| ↓ social interaction in rats | Koros et al. 2007 | ||
| ↓ burst firing activity in PFC neurons in awake rats; | Homayoun and Moghaddam 2006 | ||
| ↑ excitatory effect of MK-801 on PFC neurons | |||
| Compound 8q (PAM) | ↓ disruption of prepulse inhibition induced by amphetamine in rats | Lindsley et al. 2004 | |
| ADX47273 (PAM) | ↓ conditioned avoidance responding in rats | Liu et al. 2008 | |
| ↓ PCP- and amphetamine-induced locomotor hyperactivity in rats | |||
| ↓ dopamine levels in the nucleus accumbens | |||
| ↑ recall after a 48h delay in a novel object recognition task | |||
| CDPPB (PAM) | ↓ set-shifting impairment induced by NMDA receptor blockade in rats | Darrah et al. 2008 | |
| ↓ bursting in PFC neurons in awake rats; ↑ excitatory effect of MK-801 on PFC neurons | Lecourtier et al. 2007 | ||
| Group II | |||
| mGluR2 | Compound 5 (PAM) | ↓ ketamine-induced hyperactivity in rats | Pinkerton et al. 2005 |
| BINA (PAM) | ↓ PCP-, but not amphetamine-induced hyperactivity in mice; ↓ PCP-induced disruption in sensorimotor gating in mice | Galici et al. 2006 | |
| LY487379 (PAM) | ↓ neonatal PCP-induced deficits in social discrimination in rats | Harich et al. 2007 | |
| mGluR2/3 | LY354740 (agonist) | ↓ PCP-induced glutamate efflux in the nucleus accumbens and prefrontal cortex; ↓ PCPinduced locomotor hyperactivity in rats; ↔ dopamine levels in nucleus accumbens | Moghaddam and Adams 1998 |
| ↓ PCP-induced deficits in delayed alternation task in rats; ↓ neonatal PCP-induced deficits in social discrimination in rats | Harich et al. 2007 | ||
| ↓ performances in a delayed alternation task in rats; ↔ PCP-induced deficits in delayed alternation task in rats | Schlumberger et al. 2009 | ||
| ↓ firing rate and ↑ burst firing of pyramidal cells in the prefrontal cortex in awake rats; reverses ↑ firing rate and ↓ burst firing induced by MK-801 | Homayoun et al. 2005 | ||
| LY404039 (agonist) | ↓ PCP-induced and amphetamine-induced locomotor hyperactivity; | Rorick-Kehn et al. 2007 | |
| ↓ conditioned avoidance responding in rats | |||
| ↓ PCP-induced and amphetamine-induced locomotor hyperactivity abolished in mGluR2, but not mGluR3 knockout mice | Fell et al. 2008 | ||
| Group III | |||
| mGluR7 | AMN082 (agonist) | Prevents ↓ EPSC frequency induced by L-AP4 in dopaminergic neurons | de Rover et al. 2008 |
| ↔ basal or cocaine-induced increase in dopamine levels in the nucleus accumbens; ↔ basal or cocaine-induced locomotor hyperactivity in rats; ↓ cocaine-induced decrease in GABA levels in the ventral pallidum | Li et al. 2009 | ||
| mGluR8 | (S)-3,4-DCPG (agonist) | ↓ amphetamine-induced locomotor hyperactivity in mice when administered i.c.v.; trend to ↓ spontaneous locomotor activity | Robbins et al. 2007 |
Abbreviations and symbols: ↔, unchanged; ↑, increased; ↓, decreased; MK-801, dizocilpine maleate; PAM, positive allosteric modulator; PFC, prefrontal cortex; PCP, phencyclidine; EPSC, excitatory postsynaptic currents; i.c.v., intracerebroventricular injection.