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

Abstract

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, greater than 640; coma, 780-460; loss of righting reflex, 640-400; 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 100 mg/dl: hyperactivity, tremors, akinesia, spastic rigidity, and induced and spontaneous convulsions. A rapid sucession 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.

The effects of chronic ethanol administration on amygdala neuronal firing and ethanol withdrawal seizures

“…The neuronal firing patterns were recorded digitally. Ethanol dependence was induced by a subacute "binge" ethanol protocol (Majchrowicz, 1975) (see below). LAMG neuronal firing was recorded prior to and one hr after the first dose of ethanol administration by this protocol and during ETX.…”

“…Ethanol dependence was induced in rats by intragastric intubation of ethanol solution (Majchrowicz, 1975). Initially, each animal was given a dose of 5 g/kg of ethanol in the form of ethanol solution (30% v/v), and each subsequent dose was based on the behavior to maintain the intoxication of the rats at the mild-to-moderate ataxic state (Majchrowicz, 1975).…”

“…Initially, each animal was given a dose of 5 g/kg of ethanol in the form of ethanol solution (30% v/v), and each subsequent dose was based on the behavior to maintain the intoxication of the rats at the mild-to-moderate ataxic state (Majchrowicz, 1975). The rats were given the ethanol solution every 8 hrs for 4 days and ethanol was withdrawn at the end of the fourth day.…”

“…Audiogenic seizures (AGS) can be induced by intense acoustic stimulation during ethanol withdrawal (ETX) after a "binge" ethanol administration protocol (Majchrowicz, 1975;Riaz, 1994, 1995). The AGS in ETX rats are typically composed of a wild running episode, which is often followed by generalized clonic and/or tonic convulsions Riaz, 1994, 1995;Riaz and Faingold, 1994;Feng and Faingold, 2000;Feng et al, 2007).…”

“…The animals in the present study were subjected to chronic intermittent ethanol (CIE) administration once daily for 28 days. Microwire chronic electrodes were implanted either before or after CIE. One week after CIE the rats were treated with the 4-day "binge" ethanol protocol (Majchrowicz, 1975). LAMG neuronal responses were evaluated during CIE, one hr after the first dose of the binge ethanol, and during ETX in behaving animals.…”