Table 5.
Summary of Preclinical Studies Supporting a Role of mGluRs in Parkinson’s Disease
| Receptor Subtype | Pharmacological Tool | Effect | References |
|---|---|---|---|
| Group I | |||
| DHPG (agonist) | ↓ Amphetamine-induced rotations in 6-OHDA rats | Agari et al. 2008 | |
| mGluR1 | EMQMCM (antagonist) | ↓ Haloperidol-induced catalepsy; ↔ haloperidol-induced locomotor Hypoactivity in rats; ↔ L-DOPA-induced dyskinesias | Dekundy et al. 2006 |
| AIDA (antagonist) | ↔ L-DOPA-induced dyskinesias | Dekundy et al. 2006 | |
| LY367385 (antagonist) | Neuroprotection and rescue against 6-OHDA toxicity in rats | Vernon et al. 2005; 2007 | |
| mGluR5 | MPEP (antagonist) | ↓ Reaction time in partial bilaterally 6-OHDA-lesioned rats after chronic treatment | Breysse et al., 2002; 2003 |
| Neuroprotection and rescue against 6-OHDA toxicity in rats | Vernon et al. 2005; 2007 | ||
| ↓ Motor asymmetry in unilateral 6-OHDA-lesioned rats after STN administration | Phillips et al. 2006 | ||
| MTEP (antagonist) | ↓ Priming and expression of L-DOPA-induced dyskinesia in rats | Rylander et al. 2009;Dekundy et al. 2006 | |
| ↓ Haloperidol induced catalepsy; ; ↔ haloperidol-induced locomotor hypoactivity in rats | Dekundy et al. 2006 | ||
| SIB-1893 (antagonist) | ↓ L-DOPA-induced dyskinesias in MPTP primates; ↔ symptomatic effect of L-DOPA | Hill et al. 2001 | |
| Group II | |||
| mGluR2/3 | DCG-IV (agonist) | ↓ Reserpine-induced akinesia in rats | Dawson et al. 2000 |
| LY354740 (agonist) | ↓ Haloperidol-induced catalepsy in rats | Bradley et al. 2000 | |
| LY379268 (agonist) | ↔ Reserpine-induced akinesia in rats; ↔
rotations in 6-OHDA rats ↓ Nigrostriatal degeneration after 6-OHDA in rats |
Murray et al. 2002 | |
| ↓ Nigrostriatal degeneration after MPTP in mice | Battaglia et al. 2003 | ||
| Group III | |||
| L-AP4 (agonist) | ↓ Haloperidol-induced catalepsy; ↓ reserpine-induced akinesia in rats; ↓ forelimb asymmetry in 6-OHDA-lesioned rats | Valenti et al. 2003 | |
| ↓ Reaction time in partial bilaterally 6-OHDA-lesioned rats | Lopez et al. 2007 | ||
| Neuroprotection and rescue following 6-OHDA lesion in rats | Vernon et al. 2005; 2007 | ||
| Neuroprotection against rotenone toxicity | Jiang et al. 2006 | ||
| mGluR4 | PHCCC | ↓ Reserpine-induced akinesia in rats | Marino et al. 2003 |
| LSP1-2111 (agonist) | ↓ Haloperidol induced catalepsy in rats; ↓ reaction time in partial bilaterally 6-OHDA-lesioned rats; ↓ glutamate transmission at the striatopallidal synapse | Beurrier et al. 2009 | |
| mGluR7 | AMN082 (agonist) | ↓ Haloperidol induced catalepsy; ↓ apomorphine-induced rotations in unilateral 6-OHDA rats; ↓ reaction time deficits in bilateral 6-OHDA rats | Greco et al. 2009 |
Abbreviations and symbols: ↑, increased; ↓, decreased ; ↔, unchanged; 6-OHDA, 6- hydroxydopamine; ACh, Acetylcholine; MPTP, L-3,4-dihydroxyphenylalanine; PAM, positive allosteric modulator; STN, subthalamic nucleus.