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).