Fenofibrate

Drug or vehicle was administered prior to the drinking tests as described below. Drugs were administered either intraperitoneally (i.p.; 10mL/kg), subcutaneously (s.c.; 2mL/kg), or per os (p.o.; 5mL/kg; via FTP-20-30 20 gauge, 30 mm length plastic feeding tubes from Instech Laboratories, Inc., Plymouth Meeting, PA, USA). Table S1 specifies doses and routes of administration for each experiment.
Grain ethanol (200 proof, Decon Laboratories, Inc.) was used in all experiments. Drugs administered during ethanol drinking experiments were gabapentin (Sigma-Aldrich, Milwaukee, WI, USA), tesaglitazar (Tocris, Minneapolis, MN, USA), fenofibrate (Sigma-Aldrich, Milwaukee, WI, USA), caffeic acid phenethyl ester (CAPE; Tocris, Minneapolis, MN, USA), ibrutinib (Toronto Research Chemicals, Inc., Toronto, ON, Canda) and rolipram (Sigma-Aldrich, Milwaukee, WI, USA). The vehicle used for gabapentin and CAPE was saline (Baxter Healthcare Corporation, Deerfield, IL, USA), while for tesaglitazar, fenofibrate, and rolipram, the vehicle was saline and 1.5-2% Tween-80 (Sigma-Aldrich, Milwaukee, WI, USA). The vehicle for ibrutinib was saline, 1.75% Tween-80, and 5% DMSO in week 1, and 100% DMSO in week 2. Table S1 provides a list of drugs, doses, and mechanisms of action for each experiment.

Minocycline (50–300 μg, i.t.), fluorocitrate (0.5–1.5 nmol, i.t.), propentofylline (25–75 μg, i.t.), TNP-ATP sodium salt (5.0 μg, i.t.), (2R)-amino-5-phosphonovaleric acid; (2R)-amino-5-phosphonopentanoate (APV; 0.5 μg, i.t.), and fenofibrate (200 μg, i.t.) were purchased from Sigma. The p38 inhibitor, 4-(4-fluorophenyl)-2-(4-methylsulfonylphenyl)-5-(4-pyridyl)-1H-imidazole (SB203580; 30 μg, i.t.) and Y1036 (5 μg, i.t.) were obtained from Calbiochem. Recombinant human TrkB-Fc (three i.t. injections of 0.5 μg, 24 h apart) was purchased from R&D Systems. pioglitazone potassium salt (300 μg, i.t.) was purchased from Cedarlane. GW 9662 (2 mg/kg, i.p.) was obtained from Tocris, and administered 90 min prior to pioglitazone. GW 6471 (10 mg/kg, i.p.) was obtained from Sigma, and administered immediately prior to fenofibrate. All drugs were dissolved in physiological saline or 10–20% dimethyl sulfoxide. Doses were determined in pilot experiments. In one experiment, Minocycline was injected systemically at a dose of 25 mg/kg, i.p.

Eighty 10–12-week-old young adult male Fischer 344 × Brown Norway (F344×BN) rats were obtained from Harlan Laboratories, Inc. (Indianapolis, IN) and housed in pairs on a 12:12 h light-dark schedule with free access to food and water. All animal handling and experiments were performed in strict accordance with the NIH Guide for Care and Use of Laboratory Animals as approved by the Wake Forest School of Medicine Institutional Animal Care and Use Committee. After an acclimation period of 2 weeks, rats were randomized to 4 experimental groups (n = 20 rats/group), Group 1: sham irradiated; Group 2: fWBI; Group 3: sham irradiated + 0.2% w/w of fenofibrate (Sigma-Aldrich, St. Louis, MO) in the diet; and Group 4: fWBI + 0.2% w/w of fenofibrate in the diet. Rats received fenofibrate beginning 3 days before the start of fWBI and continuously until the end of the experiment. All rats were weighed weekly to assess their overall health.