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).