In vivo Pharmacology

RTT mice (Mecp2-/y) exhibit hindlimb clasping. Treatment with mGlu5 PAM VU0462807 ameliorates the clasping phenotype. (Gogliotti et al 2016 Hum Mol Genet)

mGlu7 PAM VU0422288 attenuates apneas or breathing pauses that are observed in Mecp2+/- mice using a whole body plethysmography recording chamber. The mGlu4 and mGlu8 PAM ADX88178 has no effect. Sample traces on the right. (Gogliotti et al 2017 Sci Transl Med)

 

 

Top: Associative learning and memory is measured as percent freezing in contextual fear conditioning assay, where a mouse is trained to associate the context with an aversive stimulus.

Bottom: Social preference is assessed by time spent with novel mouse (Stranger 2) vs familiar mouse (Stranger 1) in 3-chamber assay.

In both tasks, Mecp2+/- mice exhibit deficits, decreased percent freezing or no preference for the novel mouse. M4 PAM VU467154 and mGlu7 PAM VU0422288 both reverse these phenotypes.(Gogliotti et al 2018 J Pharmacol Exp Ther; Gogliotti et al 2017 Sci Transl Med)