GW842166x (GW) treatment attenuated 6-OHDA-induced motor deficits in the pole test and balance beam test. (a) Timeline of 6-OHDA injection, drug treatments, and behavioral tests. (b,c) In the pole test, mice injected with 6-OHDA took more time to reorient downwards (Tturn; *** p < 0.001, n = 13–13) and to descend the pole (Ttotal; *** p < 0.001, n = 13–13) compared with control mice. GW treatment prevented the prolongation of Tturn (** p = 0.004, n = 10–13) and Ttotal (** p = 0.007, n = 10–13) induced by 6-OHDA injection. The protective effects of GW were prevented by co-treatment with AM630 (AM) (Tturn, * p = 0.014; Ttotal, * p = 0.044, n = 10–11). (d) In the balance beam test, the average time to cross the beam was not significantly affected by 6-OHDA injection, chronic GW treatment, or co-treatment with GW and AM (p > 0.05, n = 10–13). (e) The number of foot slips from the beam was significantly increased in the 6-OHDA group relative to control (*** p < 0.001, n = 13–13), the increase in foot slips was attenuated by GW treatments (* p = 0.011, n = 10–13), and AM co-treatments prevented the effect of GW (* p = 0.039, n = 10–11).