, Volume 43, Issue 3, pp 245–254 | Cite as

Induction of physical dependence upon ethanol and the associated behavioral changes in rats

  • Edward Majchrowicz
Animal Studies


This paper reports findings relative to a simple, rapid and reproducible technique for the induction of physical dependence upon ethanol in the rat. The dependence was induced by intragastric intubation of 20% (w/v) ethanol solutions at 9–15 g/kg in 3–5 fractional doses daily for 4 days, maintaining blood ethanol concentrations above a threshold level sufficient to sustain observable sedation throughout the entire period of intubation. Two phases were distinguished during the withdrawal period: 1. Prodromal detoxication, characterized by a spectrum of signs and responses of diminishing severity, related to the decline in blood ethanol concentrations (mg/dl): death, >640; coma, 780–460; loss of righting reflex, 640–440; ataxia 3–1, 570–250; sedation, 340–190; neutrality, 220–130; 2. Ethanol dependence, characterized by a spectrum of withdrawal signs and reactions of progressively increasing severity as blood ehtanol concentration approached 100mg/dl: hyperactivity, tremors, akinesia, spastic rigidity, and induced and spontaneous convulsions. A rapid succession of two diverse clusters of signs and reactions represents a reversal of the central nervous system function from the extremes of ethanol intoxication (CNS depression) to the extremes of ethanol dependence (CNS hyperexcitability) during the withdrawal period. Both extremes may terminate in death.

Key words

Ethanol Ethanol Dependence Physical Dependence Induction of Ethanol Dependence Prodromal Detoxication Alcohol Withdrawal Syndrome Withdrawal Signs and Responses Blood Ethanol Levels Convulsions Tremor CNS Hyperactivity CNS Depression Assessment of Doses Intoxication-Dose Relationship Rating of Withdrawal Syndrome Spectrum and Continuum of Ethanol Intoxication and Withdrawal 


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Copyright information

© Springer-Verlag 1975

Authors and Affiliations

  • Edward Majchrowicz
    • 1
  1. 1.Laboratory of Alcohol Research, National Institute on Alcohol Abuse and Alcoholism, ADAMHA, William A. White BuildingSaint Elizabeths HospitalWashington, D.C.

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