Table 1. Phenotypes corrected by mGluR1/5 inhibition in animal models of FX^*.

Animal model	Fragile X phenotype (versus WT)	mGluR1/5 manipulation	Reference(s)
Mouse	Exaggerated mGluR-LTD	Grm5+/- cross Lithium	Dolen et al. 2007 Choi et al. 2011
Mouse	Increased AMPA receptor internalization	MPEP	Nakamoto et al. 2007
Mouse	Impaired spontaneous EPSCs in juvenile hippocampus	MPEP	Meredith et al. 2011
Mouse	Increased protein synthesis	Grm5+/- cross MPEP (mGluR5 NAM) Lithium	Dolen et al. 2007 Osterweil et al. 2010 Liu et al. 2011
Mouse	Decreased number of mRNA granules in whole brain	MPEP	Aschrafi et al. 2005
Mouse	Increased glycogen synthase kinase-3 activity	MPEP, Lithium	Min et al. 2009 Gross et al. 2010
Mouse	Increased beta amyloid	MPEP	Malter et al. 2010
Mouse	Increased dendritic spine/filopodia density	Grm5+/- cross Fenobam (mGluR5 NAM) MPEP AFQ056 (mGluR5 NAM)	Dolen et al. 2007 de Vrij et al. 2008 Su et al. 2011 Levenga et al. 2011
Mouse	Altered visual cortical plasticity	Grm5+/- cross	Dolen et al. 2007
Mouse	Exaggerated inhibitory avoidance extinction	Grm5+/- cross	Dolen et al. 2007
Mouse	Impaired eyelid conditioning	MPEP	Koekkoek et al. 2005
Mouse	Decreased initial performance on rotorod	MPEP	Thomas et al. 2012
Mouse	Associative motor-learning deficit	Fenobam	Veloz et al. 2012
Mouse	Increased audiogenic seizure	Grm5+/- cross MPEP Lithium JNJ16259685 (mGluR1NAM)	Dolen et al. 2007 Thomas et al. 2012, Yan et al. 2005 Min et al. 2009 Thomas et al. 2012
Mouse	Prolonged epileptiform discharges in hippocampus	MPEP	Chuang et al. 2005
Mouse	Increased persistent activity states in neocortex	MPEP, Grm5+/- cross	Hays et al. 2011
Mouse	Increased open-field activity	MPEP Lithium Grm1 +/- cross	Min et al. 2009, Yan et al. 2005 Thomas et al. 2011
Mouse	Defective prepulse inhibition of acoustic startle	MPEP AFQ056	de Vrij et al. 2008 Levenga et al. 2011
Mouse	Abnormal social interaction with unfamiliar mouse	Grm5+/- cross	Thomas et al. 2011
Mouse	Increased marble burying (repetitive behavior)	JNJ16259685, MPEP	Thomas et al. 2012
Mouse	Impaired presynaptic function in amygdala	MPEP	Suvrathan et al. 2010
Mouse	Avoidance behavior deficit	Fenobam	Veloz et al. 2012
Mouse	Pubertal increase in body weight	Grm5+/- cross	Dolen et al. 2007
Zebrafish	Abnormal axon branching	MPEP	Tucker et al. 2006
Zebrafish	Craniofacial abnormalities	MPEP	Tucker et al. 2006
Zebrafish	Reduced number of trigeminal neurons	MPEP	Tucker et al. 2006
Fly	Increased synaptic transmission	dmGluR-A null cross	Repicky & Broadie 2009
Fly	Increased NMJ axon arborization	dmGluR-A null cross, MPEP	Pan et al. 2008
Fly	Increased NMJ presynaptic vesicle density	dmGluR-A null cross	Pan et al. 2008
Fly	Mushroom-body structural abnormalities	MPEP, lithium	McBride et al. 2005, Pan et al. 2008
Fly	Age-dependent cognitive decline	MPEP, lithium	Choi et al. 2010
Fly	Altered regulation of ionotropic glutamate receptor subtypes	dmGluR-A null cross	Pan & Broadie 2007
Fly	Decreased courtship/social learning	MPEP, lithium	McBride et al. 2005, Tauber et al. 2011
Fly	Decreased olfactory memory	MPEP	Bolduc et al. 2008
Fly	Increased embryonic lethality on glutamate enriched diet	MPEP	Chang et al. 2008
Fly	Increased roll-over (righting) time	dmGluR-A null cross	Pan et al. 2008

^*Abbreviations: AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; EPSC, excitatory postsynaptic currents; FX, fragile X; dmGluR, drosophila mGluR; LTD, long-term depression; mGluR, metabotropic glutamate receptor; MPEP, 2-methyl-6-(phenylethynyl)-pyridine; mRNA, messenger RNA; NAM, negative allosteric modulator; NMJ, neuromuscular junction; WT, wild type.