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Table 2 Summary of Preclinical Efficacy of Group II mGlu Receptor Ligands

From: Targeting metabotropic glutamate receptors for novel treatments of schizophrenia


Positive Symptom Models

Negative Symptom Models

Cognition Models

mGlu 2/3 agonists


Reduced NMDAR-HL [127, 226]

No effect on AHL [226, 227]

Reduced NMDAR antagonist-induced stereotypies [127, 128]

No effect on apomorphine-disrupted PPI [227]

Inhibited DOI-induced head twitches [228]

Reduced PCP-induced deficits in social interaction [229]

Reduced PCP-induced deficits in the discrete-trial delayed alternation (DTDA) task [127]

Impaired performance in delayed matching to position (DMTP) and DNMTP tasks [143]


Reduced NMDAR-HL and AHL [141, 226, 230]

No effect on PCP- or AMP-disrupted PPI [141]

Inhibited DOI-induced head twitches [228]

Reduced prenatal restraint-induced HL/PPI deficits [231]

Reversed postnatal isolation-induced HL/PPI deficits [232]

Reduced MK-801-increase in immobility in forced swim test (FST) [230]

Attenuated MK-801-induced deficits in social interaction [233, 234]

Rescued prenatal restraint-induced deficits in social interaction [231]

Reduced PCP-induced increase in errors, but not accuracy, in the 5-choice serial reaction time task (5CSRT) [235]

Exacerbated PCP-induced deficits in 5CRST task [236]

Rescued MK-801-induced deficits in NOR [234]

Reversed postnatal isolation-induced deficits in NOR [232]

mGlu 2 PAMs


Reduced NMDAR-HL and AHL [141]

Attenuated AMP but not PCP-disrupted PPI [141]

Reduced PCP-induced deficits in social interaction [229]

Promoted cognitive flexibility in attentional set-shift task (ASST) [237]


Reduced NMDAR-HL [149, 230]

No effect on AHL [149]

Reduced PCP-disrupted PPI [149]

Reduced DOB-induced head twitches [150]

Reduced MK-801-induced increased immobility in the FST [230]



Reduced MHL [156]

Rescued MK-801 induced social memory deficits [156]



Reduced NMDAR-HL [158]

No effect on AHL [158]

Inhibited DOM-induced head twitches [158]



No effect on NMDAR-HL or AHL [160]

No effect on hyperactivity in DAT−/− and NR1neo−/− mice [160]

Reduced DOI-induced head twitches [160]


Reversed MK-801-induced deficits in NOR [160]

Attenuated working memory deficits in Y-maze test in NR1neo−/− mice [160]