Memantine

To investigate whether TBUS-induced plasticity effects were NMDAR-dependent, the animals were randomly assigned to three experimental groups (six animals in each group) for iTBUS and other three groups for cTBUS to receive either an acute injection of memantine (Tocris, Bristol, UK) at the dose of 5 mg/kg (6.25 ml/kg, ip), DCS (Sigma-Aldrich, St. Louis) at a dose of 3 mg/kg (10 ml/kg, ip), or saline (0.9% NaCl, ip). As MK-801 has a higher affinity for NMDARs than memantine, we used MK-801 (Tocris, Bristol, UK) at a dose of 0.1 mg/kg to further test the NMDAR dependency of TBUS-induced plasticity effects. To examine whether TBUS induces de novo protein synthesis, the animals were intraperitoneally injected with CXM (Sigma-Aldrich, St. Louis) in a 30 mg/kg (10 ml/kg, ip) dose or saline. To examine whether BDNF signaling produces TBUS-induced after-effects, we administered ANA-12 (0.5 mg/kg) (dissolved in 1% DMSO in saline, 10 ml/kg, ip) or 1% DMSO in saline. To examine whether the TrpA1 ion channel is involved in producing TBUS-induced after-effects, we administered HC-030031 (100 mg/kg) dissolved in 5% DMSO and 10% Tween 80 in saline [or HC-030031 (20 mg/kg) dissolved in 1% DMSO and 10% Tween 80 in saline].

Memantine, amantadine, ketamine, and dextromethorphan were purchased from Tocris Bioscience (Bristol, UK). The remaining substances were purchased from Sigma‐Aldrich (St Louis, MO).

PDC and memantine were obtained from Tocris (Lille, France) and Trolox from Sigma‐Aldrich (L'Isle d'Abeau Chesnes, France). Glial cell line–derived neurotrophic factor (GDNF) was from Eurobio AbCys (Courtaboeuf, France). The goat anti‐human/rat neutralizing GDNF antibody (AF‐212‐NA; RRID:AB_2111398) was purchased from R&D Systems Europe (Lille, France).