Clomipramine

clomipramine hydrochloride (clomipramine; Sigma-Aldrich, São Paulo, Brazil) and memantine hydrochloride (memantine; Sigma-Aldrich, São Paulo, Brazil) were used. All drugs were dissolved in the drinking water (memantine at 0.006 mg/ml and clomipramine at 0.06 mg/ml concentration). The solutions were changed every two days, and the amount of liquid consumed was determined by changes in the bottle weight. The total volume was divided by the number of animals in each cage, and an average of 4.9 ml/day/animal was stably observed throughout the experiments.

Male C57BL/6 mice (age, 3–4 months) received daily intraperitoneal injections of fluoxetine (10 mg/kg; Sigma-Aldrich) for 10 d. Clomipramine (10 mg/kg; Sigma-Aldrich), trazodone (40 mg/kg; Sigma-Aldrich), or an equivalent volume of saline was administered for 14 d. For ketamine, a single intraperitoneal injection (3 mg/kg; Syntec) was performed 3 h before killing. All drugs were diluted in sterile saline solution before injection.

Pimozide (cat. no. P1793; Sigma-Aldrich) was intraperitoneally (IP) administered daily at 5 mg/kg. Risperidone (cat. no. 1604654; Sigma-Aldrich) was delivered IP daily (3 mg/kg) for 2 weeks (early lesion study) or in drinking water (1.56 mg/l) until euthanasia (tumor latency study), resulting in the same daily dose based on the calculation previously reported [37 (link)]. Aripiprazole (cat. no. SML0935; Sigma-Aldrich) was delivered via IP injection in a daily dose of 3 mg/kg for 2 weeks, and clomipramine (cat. no. 1140247; Sigma-Aldrich) was delivered in drinking water (190 mg/l), resulting in a daily dose of 28 mg/kg. All drugs were diluted in dimethyl sulfoxide (DMSO) to the appropriate concentrations. Both ruxolitinib and control chow was provided by Incyte Corp. Ruxolitinib chow was packaged in a pre-determined measurement of 2000 mg/kg chow; mice were allowed to free-feed for the duration of the study.

Niclosamide ethanolamine was purchased from Cayman Chemical; domperidone, imipramine, amitriptyline, desipramine, and clomipramine were purchased from Sigma‐Aldrich.

Fluoxetine (#H6995, Bosche Scientific), citalopram (#C505000, Toronto Research Chemicals), paroxetine (#2141, Tocris), fluvoxamine (#1033), venlafaxine (#2917, Tocris), reboxetine (#1982, Tocris), imipramine (#I7379-5G, Sigma–Aldrich), clomipramine (#C7291, Sigma–Aldrich), desipramine (#3067, Tocris), phenelzine (#P6777, Sigma–Aldrich), rolipram (#R6520, Sigma–Aldrich), ketamine (#3131, Tocris), 2R, 6R-Hydroxynorketamine and 2S, 6S-Hydroxynorketamine (#6094 and #6095, respectively, Tocris), carbamazepine (#4098, Tocris), chlorpromazine (#C8138, Sigma–Aldrich), flupenthixol (#4057, Tocris), and pimozide (#0937, Tocris) were investigated in this study. The compounds were dissolved in dimethyl sulfoxide (DMSO) that was also used as a vehicle in all the experiments. Concentrations tested (Table 1) were selected based on earlier in vitro studies from our research group (Fred et al., 2019 (link); Casarotto et al., 2021 (link)) and other laboratories (Johansen et al., 2015 (link)).