As reviewed in the clinical treatment section, mGlu2/3 agonists are a promising treatment for schizophrenia, but mGlu2 positive allosteric modulators may produce equivalent efficacy with less susceptibility to downregulation. In this study [37], pretreatment with biphenyl indanone-A suppressed the amplitude of the blood oxygen level-dependent response to PCP in the prefrontal cortex, caudate–putamen, nucleus accumbens, and mediodorsal thalamus. This was consistent with the a-priori hypothesis, and suggests that selective mGlu2 agonism may be efficacious on its own, as opposed to the more widely studied nonselective mGlu2/3 agents.
