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18 protocols using oxycodone

1

Oxycodone Self-Administration in Mice

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A 2-h self-administration session was conducted daily. Mice were weighed and heparinized saline solution (0.02 ml of 30 IU/ml) was used daily to flush the catheter to maintain patency. During self-administration sessions, mice in the oxycodone (Sigma, St. Louis, MO, USA) groups were placed in the self-administration chamber and a nose-poke through the active hole led to an infusion of oxycodone (0.25 mg/kg/infusion) under an FR1 schedule for 14 days. Drug volume was controlled by a computer to follow daily changes in body weight of individual animals. Mice in the control groups received yoked saline infusions during all sessions (saline was infused in the control mouse whenever the oxycodone mouse self-administered oxycodone). At the end of the experiment, only data from mice that passed a catheter patency test (defined as loss of muscle tone within a few seconds after administration of a short-acting anesthetic) with injection of 30 μl of ketamine (5 mg/ml) (Fort Dodge, IA) were included in the analysis of data. See also Mayer-Blackwell et al. (2014) (link).
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2

Quantifying Opioid Transport Across BMEC

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Morphine, oxycodone and loperamide were purchased from Sigma-Aldrich and applied to the vascular chamber at 41 µg/ml (143.7 µM) Morphine, 10 µg/ml (31.7 µM) oxycodone, or 1.5 µg/ml (3.1 µM) loperamide. These concentrations were chosen as those closest to physiological that could still be reliably detected after transport [17 (link)]. Each drug was perfused through the vascular chamber for 24 h to establish equilibrium. Perfusion with drug was then continued over a 1 h period, with active sample collection from both the vascular and brain chambers (120 µl total from each compartment). Samples were stored at − 80 °C until processing for mass spectrometry analysis. Opioid transport was calculated as the amount of opioid detected in the brain chamber compared to the total amount of opioid delivered to the vascular chamber (percent of opioid transported across the BMEC monolayer).
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3

Oxycodone Self-Administration in Mice

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A 2-hr self-administration session was conducted once a day. Each day, mice were weighed and the catheter flushed with heparinized saline (0.01 ml of 30 IU/ml solution) to maintain patency. During each of the 14 self-administration sessions, mice in the oxycodone (Sigma, St. Louis, MO) groups received an infusion of oxycodone (0.25 mg/kg/infusion) under an FR1 schedule following each active hole nose poke. During all sessions, mice in the yoked control groups received a saline infusion (20 μl/inf) when the oxycodone mouse self-administered oxycodone.
At the end of the self-administration experiment, only data from mice that passed a catheter patency test [defined as loss of muscle tone within a few seconds after i.v. administration of 30 μl of ketamine (5 mg/ml; Fort Dodge, IA)] were included in the analysis of self-administration data. Of a total 346 mice that started the study, 217 mice finished the 14-day self-administration study and passed the catheter patency test. Of these 217 mice, 130 mice finished the conditioned place preference study, and 84 mice finished the anti-nociception study, 3 mice were not included in either study because of health issues.
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4

Pharmacokinetic Evaluation of Analgesic Compounds

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remifentanil hydrochloride, oxycodone hydrochloride, and naltrexone hydrochloride were obtained from (Sigma-Aldrich, St. Louis, Missouri) and were dissolved in saline (remifentanil, oxycodone) or sterile water (naltrexone). ML375 was synthesized in house as described previously58 (link) and formulated as a macrosuspension in 5% dimethylsulfoxide (Sigma) and 20% (w/v) hydroxypropyl-β-cyclodextrin (Trappsol, CTD, Inc., Alachua, Florida) and administered intraperitoneally (i.p.) in a volume of 2–4 mL/kg.
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5

Oxycodone-Induced Conditioned Place Preference and Analgesia

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Oxycodone was purchased from Sigma Chemical or Toronto Research Chemicals, or it was provided as a gift by the US National Institute for Drug Abuse. It was diluted in sterile saline to achieve a dose of 3 mg/kg for i.p. injections at a volume of approximately 0.5 mL for CPP and the tail-flick test, and 0.1 mg/kg per infusion for self-administration.
During CPP and the tail-flick test, maraviroc (Glentham Life Science) was dissolved in sterile saline for i.p. injections of 10 mg/kg. For the Oxycodone-seeking test, maraviroc was dissolved in 8% dimethyl sulfoxide, 30% polyethylene glycol 400, 30% Tween 80 and H2O. The vehicle was 8% dimethyl sulfoxide, 30% polyethylene glycol 400, 5% Tween 80 and H2O. The drug doses we used were based on relevant literature (Oxycodone24 (link)) and preliminary experiments in our laboratories.
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6

Intravenous Oxycodone and Cocaine Administration

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Oxycodone (Sigma-Aldrich) is dissolved in 0.9% sterile saline (Hospira) and administered at 150 μg/kg per infusion intravenously. Cocaine HCl (National Institute on Drug Abuse, Bethesda, MD) is dissolved in 0.9% sterile saline and administered intravenously at a dose of 0.5 mg/kg per infusion.
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7

Pharmacological Modulation of Behavior

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d-Amphetamine (dextroamphetamine hemisulfate), scopolamine (scopolamine hydrobromide), and oxycodone (oxycodone hydrochloride) were obtained from Sigma-Aldrich (St. Louis, MO). All drugs were dissolved in 0.9% saline solution and were administered via subcutaneous injection in volumes of 1 ml/kg or less. Drug doses (mg/kg) are expressed in terms of their free base weights.
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8

Δ9-THC and Oxycodone Combination Protocol

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Δ9-THC (NIDA drug supply program) was provided in ethanol (200 mg/ml), and dissolved in a vehicle of 4.75% ethanol, 5% Koliphor EL, and 90% sterile saline and administered at volume of 5 ml/kg. For this vehicle, a stock of Koliphor and saline was separately mixed and then added to the corresponding amount of ethanol to yield the final injectable vehicle. Oxycodone (Sigma-Aldrich) was dissolved in sterile saline and administered at a volume of 5 ml/kg. For experiments which involved combinations of Δ9-THC and Oxycodone both compounds were dissolved in the same vehicle (4.75% ethanol, 5% Koliphor EL and 90% sterile saline) at 2.5 ml/kg. Equal parts of each solution were combined to generate Δ9-THC and Oxycodone cocktail which was injected at a volume of 5 ml/kg.
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9

Antibiotic Cocktail Depletion Protocol

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Oxycodone (Sigma-Aldrich) was dissolved in 0.9% sodium chloride (Hospira) and administered subcutaneously (2 mg/kg) every 12 h. Naloxone (Sigma-Aldrich) was dissolved in 0.9% sodium chloride (Hospira) and administered subcutaneously (1 mg/kg). Antibiotic doses were given at the following concentrations in drinking water according to a previous study (Kiraly et al., 2016 (link)): bacitracin (0.5 mg/ml), neomycin (2 mg/ml), vancomycin (0.2 mg/ml), and pimaricin (1.2 μg/ml). These antibiotics were selected because they are absorbed in the intestine and have been previously reported to only have efficacy in depleting the microbiome when administered orally. The antibiotic mixture was changed every 2 d. The rats were weighed weekly to ensure the maintenance of body weight.
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10

Oxycodone Dosage Preparation Protocol

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Oxycodone was obtained from Sigma (St. Louis, MO) and doses are expressed as the weight of the base.
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