Operant Self‐Administration Models for Testing the Neuropharmacological Basis of Ethanol Consumption in Rats

Harry L. June1, Nicholas W. Gilpin2

1 University of Maryland School of Medicine, Baltimore, Maryland, 2 The Scripps Research Institute, La Jolla, California
Publication Name:  Current Protocols in Neuroscience
Unit Number:  Unit 9.12
DOI:  10.1002/0471142301.ns0912s51
Online Posting Date:  April, 2010
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Abstract

Operant self‐administration procedures are used to assess the neural basis of ethanol‐seeking behavior under a wide range of experimental conditions. In general, rats do not spontaneously self‐administer ethanol in pharmacologically meaningful amounts. This unit provides a step‐by‐step guide for training rats to self‐administer quantities of ethanol that produce moderate to high blood‐alcohol content. Different protocols are used for rats that are genetically heterogeneous versus rats that are selectively bred for high alcohol preference. Also, these protocols have different sets of advantages and disadvantages in terms of the ability to control for caloric intake and taste of solutions in operant testing. Basic self‐administration protocols can also be altered to focus on different aspects of the motivational properties of ethanol (for example, those related to dependence). This unit provides multiple protocols that lead to alcohol intake in rats, which can be pharmacologically probed relative to a variety of control conditions. Curr. Protoc. Neurosci. 51:9.12.1‐9.12.26. © 2010 by John Wiley & Sons, Inc.

Keywords: ethanol; alcohol; self‐administration; neuropharmacology; operant learning

     
 
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Table of Contents

  • Introduction
  • Strategic Planning
  • Basic Protocol 1: Train Rats to Initiate Ethanol‐Maintained Responding on an FR‐4 Schedule
  • Support Protocol 1: Blood Alcohol Content (BAC)
  • Support Protocol 2: Training Rats to Respond for Ethanol on a Progressive‐Ratio Schedule
  • Support Protocol 3: Testing Ethanol Self‐Administration Behavior in Alcohol‐Dependent Rats
  • Basic Protocol 2: Train Rats to Initiate Saccharin‐Maintained Responding on an FR‐4 Schedule
  • Basic Protocol 3: Train Rats to Lever Press Concurrently for Ethanol and Saccharin Under an FR‐4 Schedule
  • Basic Protocol 4: Train Rats to Lever Press Concurrently for Alcohol and an Isocaloric Alternative Solution Under an FR‐4 Schedule
  • Basic Protocol 5: Train Rats to Initiate Binge‐Like Ethanol Responding in an Operant Situation
  • Commentary
  • Literature Cited
  • Figures
     
 
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Materials

Basic Protocol 1: Train Rats to Initiate Ethanol‐Maintained Responding on an FR‐4 Schedule

  Materials
  • Ten 2‐ to 3‐month‐old naïve outbred rats or rats selectively bred for alcohol consumption (∼200 to 300 g, female or male)
  • Standard rodent diet
  • 0.10% (w/v) saccharin (Fisher Scientific) solution in distilled water
  • 2% (v/v) ethanol/0.075% (w/v) saccharin solution
  • 5% and 10% (v/v) ethanol solutions
  • Wire‐mesh stainless‐steel cages or plastic tubs
  • Personal computer with standard operant software packages (e.g., from Coulbourn Instruments or Med Associates) to record responses and control reinforcements
  • Stopwatch
  • Ten standard operant chambers (Coulbourn Instruments; Fig. A) equipped with two removable levers (Fig. B) and two dipper fluid delivery systems (Fig. C) enclosed in sound‐attenuated cubicles (Fig. D)
  • Animal balance for weighing rats
NOTE: Dipper presentations should provide 1.5‐sec access to a 0.10‐ml dipper solution, followed by a 3‐sec time‐out period; the amount of the earned reinforcer delivered following the various response requirements in Basic Protocols protocol 11 to protocol 74 is 0.10 ml. Above each lever, a stimulus light (red, green, or yellow) is present and is illuminated upon presentation of the stimulus delivery/reinforcer (Fig. B).

Support Protocol 1: Blood Alcohol Content (BAC)

  Materials
  • Rats (see Basic Protocols protocol 11 to protocol 74)
  • Heparin‐coated microcentrifuge tubes
  • Microcentrifuge
  • Clinical analyzer (GL‐5 MicroStat, Analox Instruments)
  • Clark‐type amperometric oxygen electrode
  • Additional reagents and equipment for collecting blood from the rat's tail (Donovan and Brown, )
NOTE: Use alcohol reagent buffer solutions (pH 7.4) and alcohol oxidase enzymes provided by the manufacturer (Analox Instruments) in all samples tested.

Support Protocol 2: Training Rats to Respond for Ethanol on a Progressive‐Ratio Schedule

  • 10% (w/v) sucrose solution

Support Protocol 3: Testing Ethanol Self‐Administration Behavior in Alcohol‐Dependent Rats

  • Glucose‐saccharin (“Supersac”) solution: 3% glucose + 0.0125% saccharin in water
  • Sweetened alcohol: 10%(w/v) ethanol + 3% glucose + 0.0125% saccharin in water
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Figures

Videos

Literature Cited

Literature Cited
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