Nigral perfusion with VU0152100 alleviated LID and its
neurochemical correlates whereas nigral perfusion with PD-102807 was
ineffective
Nigral M4 receptors activated by cholinergic afferents from the PPN
exert a powerful modulation of D1 receptor signaling at striato-nigral
MSNs terminals in SNr (Moehle et
al. , 2017). To prove this modulation is relevant to LID, VU0152100
(100 µM) or PD-102807 (3 µM) were perfused through the probe implanted
in SNr. Nigral perfusion with VU0152100 reduced LID by
~60%, whereas PD-102807 was ineffective (H=16.50
p=0.0003 Fig. 6A). Intranigral VU0152100 also inhibited the
LID-associated rise of nigral GABA (F2,21=18.34,
p<0.0001; Fig.6B) and Glu (F2,21=4.99,
p=0.0168; Fig. 6C) and, differently from striatal perfusion, also the
LID-associated rise of Glu in striatum
(F2,21=6.31,
p=0.0071; Fig. 6D). Consistent with its failure in modulating LID,
intranigral PD-102807 did not influence the LID-associated increase of
nigral GABA (F2,21=5.52, p=0.0118; Fig. 6E) and Glu
(F2,21=4.860, p=0.0184; Fig. 6F).