Figure 4.

VU6021625 reversed muscarinic-induced deficits in dopamine release and signaling. (A) Sample traces of miniature inhibitory postsynaptic currents (mIPSCs) during baseline (top) and following the bath application of 10 μM VU6021625 (bottom). (B) Inhibition of M₄ activity by VU6021625 significantly increased mIPSC frequency (paired t test, *p < 0.05, n = 5 cells). (C) Sample traces of mIPSCs during baseline (top), bath application of the nonselective mAChR agonist oxotremorine-M (Oxo-M) (middle), or bath application of 10 μM Oxo-M + VU6021625 (bottom). Bath application of VU6021625 completely blocked the change in frequency induced by Oxo-M, paired t test, **p < 0.01 (C–D, n = 5–7 cells/group). Sample traces (E) and time-courses (F) of Oxo-M-induced inhibition of DA release in the absence or presence of the M4-selective antagonist VU6021625. (G) Bar graph summary depicting the % inhibition of DA release observed under different conditions from 30 to 40 min (n = 6–7, * p < 0.005, two tailed Mann–Whitney test, n = 5–7 slices per group). (H) Time-course of M4-mediated effects obtained from subtracting the mean values for the time-course in absence of antagonist from the mean values of the time-course in the presence of VU6021625.