The Majchrowicz Binge Alcohol Protocol: An Intubation Technique to Study Alcohol Dependence in Rats

Carl L. Faingold1

1 Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, Illinois
Publication Name:  Current Protocols in Neuroscience
Unit Number:  Unit 9.28
DOI:  10.1002/0471142301.ns0928s44
Online Posting Date:  July, 2008
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Abstract

Binge drinking of alcohol is an important public health issue, and experimental studies are needed to understand the pathophysiological mechanisms of this problem and develop improved approaches to treatment. This unit presents a validated and widely used method to model binge alcohol drinking in rats. It consists of three daily intragastric administrations of ethanol to rats for 4 days. Ethanol is initially administered at 5 g/kg, and then each subsequent dose is determined based on the degree of intoxication the rat exhibits prior to each dose. The behavior of the animal is graded based on a well‐described scale. After the fourth day, various aspects of the ethanol withdrawal syndrome can be observed over a predictable time course and additional protocols can be employed to study mechanisms of specific aspects of withdrawal and treatments to prevent them. One specific behavior observed during ethanol withdrawal and described here is sound‐induced (audiogenic) convulsive seizure. Curr. Protoc. Neurosci. 44:9.28.1‐9.28.12. © 2008 by John Wiley & Sons, Inc.

Keywords: alcohol; ethanol withdrawal syndrome; binge; intragastric intubation; audiogenic seizures

     
 
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Table of Contents

  • Commentary
  • Literature Cited
  • Figures
  • Tables
     
 
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Materials

Basic Protocol 1:

  Materials
  • Sprague‐Dawley rats (male or female), weighing 200 to 400 g (e.g., Harlan World Headquarters)
  • Rodent food pellets
  • Ethanol (USP 95%)
  • Infant formula powder [Similac Low‐iron Infant Formula Powder; Abbott/Ross Nutrition (or similar product)]
  • Vehicle (e.g., normal saline)
  • Drug to be tested
  • Mesh gloves for handling rats (e.g., Braintree Scientific)
  • Animal scale
  • Gastric intubation needle with a bulbous end (e.g., Stoelting, cat. no. 57903 which is curved, 18‐G and 3‐in. long)
  • Blood ethanol concentration equipment including (optional):
    • Vacutainer tubes
    • Blood analyzer via commercial laboratory
  • Electrical bell [e.g., AMSECO, A Potter Brand Model PBD128 (8‐in. diameter)]
  • Decibel meter (e.g., Bruel and Kjaer Meter, Model No. 1613) to calibrate electrical bell
  • Ear protection for humans in the vicinity of the acoustic stimulation experiments
  • Cylindrical chamber (clear, ∼40‐cm i.d., ∼ 38.1‐cm high) made of Plexiglas, fabricated in‐house
  • Video recording equipment
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Figures

Videos

Literature Cited

Literature Cited
   Browning, R.A. 1994. Anatomy of generalized convulsive seizures. In Idiopathic Generalized Epilepsies—Clinical, Experimental and Genetic Aspects (A. Malafosse, P. Genton, E. Hirsch, C. Marescaux, D. Broglin, and R. Bernasconi, eds.) pp. 399‐413. John Libbey and Co., New York.
   Faingold, C.L. 2004. Emergent properties of CNS neuronal networks as targets for pharmacology: Application to anticonvulsant drug action. Prog. Neurobiol. 72:55‐85.
   Faingold, C.L. and Riaz, A. 1994. Increased responsiveness of pontine reticular formation neurons associated with audiogenic seizure susceptibility during ethanol withdrawal. Brain Res. 663:69‐76.
   Faingold, C.L., N'Gouemo, P., and Riaz, A. 1998. Ethanol and neurotransmitter interactions—From molecular to integrative effects. Prog. Neurobiol. 55:509‐535.
   Falk, J.L., Samson, H.H., and Winger, G. 1972. Behavioral maintenance of high concentrations of blood ethanol and physical dependence in the rat. Science 177:811‐813.
   Feng, H.J., Yang, L., and Faingold, C.L. 2007. Role of the amygdala in ethanol withdrawal seizures. Brain Res. 1141:65‐73.
   Gonzalez, L.P., Czachura, J.F., and Brewer, K.W. 1989. Spontaneous versus elicited seizures following ethanol withdrawal: Differential time course. Alcohol 6:481‐487.
   Grahame, N.J. and Cunningham, C.L. 2002. Intravenous self‐administration of ethanol in mice. Curr. Protoc. Neurosci. 19:9.11.1‐9.11.11.
   Jobe, P.C., Mishra, P.K., and Dailey, J.W. 1992. Genetically epilepsy‐prone rats—Actions of antiepileptic drugs and monoaminergic neurotransmitters. In Drugs for Control of Epilepsy—Actions on Neuronal Networks Involved in Seizure Disorders (C.L. Faingold and G.H. Fromm, eds.) pp. 253‐276. CRC Press, New York.
   Leppel, K. 2006. College binge drinking: Deviant versus mainstream behavior. Am. J. Drug Alcohol Abuse 32:519‐525.
   Majchrowicz, E. 1975. Induction of physical dependence upon ethanol and the associated behavioral changes in rats. Psychopharmacologia 43:245‐254.
   Miller, J.W., Naimi, T.S., Brewer, R.D., and Jones, S.E. 2007. Binge drinking and associated health risk behaviors among high school students. Pediatrics 119:76‐85.
   N'Gouemo, P., Caspary, D.M., and Faingold, C.L. 1996. Decreased GABA effectiveness in the inferior colliculus neurons during ethanol withdrawal in rats susceptible to audiogenic seizures. Brain Res. 724:200‐204.
   Riaz, A. 1993. Audiogenic seizures during ethanol withdrawal changes in amino acid neurotransmission and neuronal response patterns in the inferior colliculus and the brainstem reticular formation. Dissertation. Southern Illinois University School of Medicine, Springfield, Ill.
   Samson, H.H. and Czachowski, C.L. 2003. Behavioral measures of alcohol self‐administration and intake control: Rodent models. Int. Rev. Neurobiol. 54:107‐143.
   Yang, L., Long, C., Randall, M.E., and Faingold, C.L. 2003. Neurons in the periaqueductal gray are critically involved in the neuronal network for audiogenic seizures during ethanol withdrawal. Neuropharmacology 44:275‐281.
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