Table 4.
Summary of Preclinical Studies Supporting a Role of mGluRs in Major Depression Disorder and Anxiety
| Receptor Subtype | Pharmacological Tool | Effect | References |
|---|---|---|---|
| Group I | |||
| mGluR1 | JNJ16259685 (antagonist) | ↓ Anxiety-like behaviour in the rat lick suppression test | Steckler et al. 2005 |
| AIDA (antagonist) | ↓ Anxiogenic behaviour in the rat light-dark test and open-field test | Mikulecka and Mares 2009 | |
| mGluR5 | MPEP (antagonist) | ↓ Anxiogenic behaviour in elevated-plus maze, social exploration, fear-potentiated startle, Vogel-conflict and light-dark box test | Ballard et al. 2005; Spooren et al. 2000; Spooren and Gasparini 2004; Tatarczynska et al. 2001; Mikulecka and Mares 2009; Spanka et al. 2010 |
| MTEP (antagonist) | ↓ Anxiogenic behaviour contextual fear conditioning | Gravius et al. 2008 | |
| MPEP & MTEP (antagonists) | ↓ Immobility time in the tail-suspension test and forced-swim test | Tatarczynska et al. 2001; Palucha et al. 2005; Belozertseva et al. 2007; Li et al. 2006 | |
| Antidepressant-like effects in the olfactory bulbectomy model | Palucha et al. 2005;Pilc et al. 2002 | ||
| Group II | |||
| mGluR2/3 | LY341495 (antagonist) | ↑ Firing rate of serotonergic dorsal raphe neurones | Kawashima et al. 2005 |
| MGS0039 (antagonist) | ↑ Firing rate of serotonergic dorsal raphe neurones | Kawashima et al. 2005 | |
| ↑ Extracellular levels of serotonin in the rat prefrontal cortex | Karasawa et al. 2005 | ||
| LY341495 & MGS0039 (antagonists) | ↓ Immobility and in the tail-suspension test and forced-swim test | Witkin et al. 2007; Chaki et al. 2004 | |
| LY341495 (antagonist) | Effective in the marble burying test ↔ Anxiogenic behaviour in elevated plus maze and stress-induced hyperthermia tests | Bespalov et al. 2008 | |
| MGS0039 (antagonist) | ↓ Anxiogenic behaviour in the conditioned fear model | Yoshimizu et al. 2006 | |
| Group III | |||
| ACPT-I (agonist) | ↓ Immobility time in the forced-swim test | Tatarczynska et al. 2002; Palucha et al. 2004c; Klak et al. 2007 | |
| ↓ Anxiogenic behaviour in the stress-induced hyperthermia, elevated plus-maze tests and in the Vogel test | Stachowicz et al. 2009 | ||
| mGluR4 | PHCCC (PAM) | ↓ Immobility time in the forced-swim test | Klak et al. 2007 |
| mGluR7 | AMN082 (agonist) | ↓ Immobility time in the forced swim test and tail suspension test | Palucha et al. 2007 |
| mGluR8 | RSPPG (agonist) | ↓ Immobility time in the forced-swim test | Palucha et al. 2004b |
Abbreviations and symbols: ↔, unchanged; ↑, increased; ↓, decreased; PAM, positive allosteric modulator.