Striatal perfusion with VU0152100 alleviated LID and inhibited nigral GABA and striatal Glu release
Experimental evidence in mice and non-human primates showed that M4 receptor activation with M4 PAMs palliates LID (Shen et al. , 2015). In order to confirm this finding in rats and reveal the associated pathways, we perfused the M4 receptor PAM VU0152100 at 100 µM through the probe implanted in striatum. Striatal perfusion of VU0152100 reduced LID by ⁓40% (U=7.50, p=0.0076; Fig.4A), and prevented the LID-associated nigral GABA (F2,21=7.06, p=0.0045; Fig. 4B) and Glu (F2,21=6.25, p=0.0074; Fig. 4C) surge. Unlike M4 preferential antagonists, intrastriatal VU0152100 did not affect the LID-associated increase of striatal Glu release (F2,21=4.15, p=0.0302; Fig. 4D).