Vilazodone suppressed the development of L-DOPA-induced dyskinesia and turning behavior, but not stepping improvement, after dopamine depletion by 6-OHDA. (A) Dopamine depletion (i.e., loss of striatal tyrosine hydroxylase labeling) in the different treatment groups. Representative coronal section from the mid-level striatum labeled with tyrosine hydroxylase immunohistochemistry in a rat with a 6-OHDA lesion on the right side (left) and mean density values (mean ± SEM) for tyrosine hydroxylase labeling on the side of the lesion (% of intact side) (right) are hown for groups that received a sham lesion (Sham/Veh/Veh) or a 6-OHDA lesion followed by repeated vehicle treatments (6-OHDA/Veh/Veh), repeated treatment with vilazodone (10 mg/kg, i.p.) + vehicle (3 weeks) (6-OHDA/VIL/Veh), with vehicle + L-DOPA (5 mg/kg + benserazide, 12.5 mg/kg; 3 weeks) (6-OHDA/Veh/LD), or with vilazodone + L-DOPA (6-OHDA/VIL/LD). (B) Stepping test (week 3). The number of steps (mean ± SEM) with the forelimb ipsilateral to the lesion (linked to the intact striatum) and the forelimb contralateral to the lesion (linked to the dopamine-depleted striatum) in the stepping test are given for these treatment groups. L-DOPA improved stepping with the affected (contralateral) forelimb (prokinetic effect); this improvement was not impaired by vilazodone. (C) L-DOPA-induced abnormal involuntary movements (AIMs) (week 2; 3-day averages). AIMs (axial, limb, orolingual (ALO); total) scores in the 3-h test are shown for groups with a 6-OHDA lesion followed by vehicle treatments (6-OHDA/Veh/Veh), by vehicle + L-DOPA treatment (6-OHDA/Veh/LD), or by vilazodone + L-DOPA treatment (6-OHDA/VIL/LD). Vilazodone suppressed L-DOPA-induced AIMs. (D) L-DOPA-induced turning in the open-field test (week 3). Number of half-turns contraversive (left) or ipsiversive to the lesion (right) during time periods 5–10 min (i.e., before L-DOPA effects appeared in all but one animal) and 25–40 min after L-DOPA injection are given for groups with a 6-OHDA lesion followed by vehicle + L-DOPA treatment (6-OHDA/Veh/LD) or by vilazodone + L-DOPA treatment (6-OHDA/VIL/LD). Vilazodone suppressed L-DOPA-induced contraversive turning but not “spontaneous” ipsiversive turning. ###
p < 0.001 vs. same group on intact side; *** p < 0.001 vs. Sham/Veh/Veh; φφ
p < 0.01, φφφ
p < 0.001 vs. 6-OHDA/Veh/Veh; +++
p < 0.001 vs. 6-OHDA/VIL/Veh; $$
p < 0.01, $$$
p < 0.001 vs. 6-OHDA/Veh/LD.