A Choice‐Based Screening Method for Compulsive Drug Users in Rats

Magalie Lenoir1, Eric Augier1, Caroline Vouillac1, Serge H. Ahmed1

1 Université de Bordeaux, CNRS, Institut des Maladies Neurodégénératives, Bordeaux
Publication Name:  Current Protocols in Neuroscience
Unit Number:  Unit 9.44
DOI:  10.1002/0471142301.ns0944s64
Online Posting Date:  July, 2013
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We describe a protocol for screening compulsive drug users among cocaine self‐administering rats, the most frequently used animal model in addiction research. Rats are first trained on several alternating days to self‐administer either cocaine (i.v.) or saccharin‐sweetened water (by mouth)—a potent, albeit nonessential, nondrug reward. Then rats are allowed to choose between the two rewards over several days until the preference stabilizes. Most rats choose to stop using cocaine and pursue the alternative reward. Only a minority of Wistar strain rats (generally 15%) persist in taking the drug, regardless of the severity of past cocaine use and even when made hungry and offered the possibility to relieve their physiological need. Persistence of cocaine use in the face of a high‐stakes choice is a core defining feature of compulsion. This choice‐based screening method for compulsive drug users is easy to implement, has several important applications, and compares well with other methods in the field. Curr. Protoc. Neurosci. 64:9.44.1‐9.44.17. © 2013 by John Wiley & Sons, Inc.

Keywords: addiction; animal model; choice; cocaine; saccharin; screening

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Table of Contents

  • Introduction
  • Basic Protocol 1: A Choice‐Based Screening Procedure (CBS) for Rats
  • Alternate Protocol 1: Evaluation of the Delay of Reward Action on Choice
  • Alternate Protocol 2: Effects of Reward Cost on Choice
  • Alternate Protocol 3: Discrete‐Trials Choice Procedure During Drug Intoxication
  • Commentary
  • Literature Cited
  • Figures
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Basic Protocol 1: A Choice‐Based Screening Procedure (CBS) for Rats

  • Laboratory rats of any conventional outbred strain (e.g., Wistar‐Han), 250 to 300 g (e.g., Charles River Laboratories)
  • Heparinized saline [280 IU/ml heparin (e.g., Sanofi‐Synthelabo) in sterile physiological saline (0.9%, USP, pH 7.4)]
  • Antibiotic for prophylactic treatment [e.g., 100 mg/ml ampicillin (e.g., Panpharma) in heparinized saline]
  • 70% ethanol
  • Bags of sterile physiological saline for drug dissolution (NaCl 0.9% USP, pH 7.4)
  • Cocaine hydrochloride (e.g., Coopération Pharmaceutique Française) or any other drugs of abuse that are deliverable intravenously
  • Water sweetened with sodium saccharin [e.g., 0.2% (w/v) saccharin sodium salt hydrate, Sigma Aldrich]
  • Short‐acting nonbarbiturate anesthetic for checking catheter patency (e.g., Etomidate, 1 mg/kg, i.v., Braun Medical)
  • Surface disinfectant for cleaning operant chambers (e.g., Phagozyme, Phagogène)
  • Syringe filters (0.22 µm) for preparation of drug solutions
  • Operant chambers, 30 × 40 × 36 cm (e.g., Imetronic, Pessac, France; see Internet Resources and Fig. ) and controls
    • Two opaque operant panels on the right and left sides (Fig. B)
    • Two clear polycarbonate walls on the rear and front sides (the front side corresponds to the entry/exit of the chamber) (Fig. A,B)
    • Grid floor (stainless‐steel rods of 0.6‐cm diameter spaced 1.6 cm apart from center to center) that allows waste collection in a removable tray containing maize sawdust (Fig. A,B)
    • Two automatically retractable levers (e.g., 2 × 4 × 1 cm, Imetronic), each mounted on the midline of an operant panel and 7 cm above the grid (4 in Fig. A,B)
    • Two white light diodes (1.2 cm outer diameter, one above each lever) mounted 8.5 cm above the levers to signal reward delivery (3 in Fig. A)
    • One fluid dispenser (e.g., a cylindrical drinking spout) mounted 9.5 cm to the left of the lever and 6 cm above the grid and coupled to a lickometer circuit (Imetronic) for monitoring and recording of licking (5 in Fig. A,B)
    • Wooden cubicles, equipped with a white noise speaker (45 ± 6 dB) for sound attenuation and an exhaust fan for ventilation, to enclose operant chambers
    • Two automatically controlled syringe pumps (one for i.v. drug delivery, the other for supplying the fluid dispenser) placed outside, on the top of the cubicle (1 and 2 in Fig. A)
    • Two infusion lines, one for i.v. drug self‐administration (e.g., Tygon tubing, Cole Parmer), the other for oral saccharin self‐administration (e.g., Silastic tubing, DowCorning Corporation)
    • One stainless‐steel spring (e.g., Aquitaine Ressort, France), which is suspended in the center of the chamber from the swivel tether connector, to protect the Tygon tubing (6 in Fig. A)
    • One single‐channel liquid swivel (e.g., Lomir Biomedical)
    • One swivel tether connector (e.g., Lomir Biomedical)
    • One counterbalancing device (e.g., a weight‐pulley device) to allow free movement during behavioral testing
    • Two pairs of infrared beams above the grid floor to measure forward locomotion (e.g., both pairs cross the chamber on its length axis and are separated from each other by 16 cm and from the right or left wall by 12 cm, Imetronic) (7 in Fig. B)
    • Infrared video camera mounted on the top of the chamber for behavioral observations
    • Computer for operating the operant chambers (e.g., Imetronic)
    • Electronic interface for the communication between testing chambers and computer (e.g., Imetronic)
    • Computer software for experiment programming (e.g., Imetronic)
    • Uninterruptible power supply (e.g., American Power Conversion Corp.)
  • Statistical analysis software (e.g., Statistica, StatSoft Inc, or any standard statistical software)
  • Additional reagents and equipment for jugular catheter construction, catheter flusher construction, and catheter implantation (see unit 9.20).
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Key Reference
  UNIT 9.20
  This unit is a detailed tutorial for performing chronic intravenous drug self‐administration in rats and mice.
Internet Resources
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