Animal models of the anxiogenic effects of ethanol withdrawal

Abstract

Although anxiety is a major feature of ethanol withdrawal (EW) and much of treatment related to EW is focused on amelioration of the anxiety experienced during EW, less attention has been given to the anxiogenic effects of EW than to the convulsant effects. In this article, we review the animal literature on the anxiogenic effects of EW. Both GABA A and serotonin (5-HT) receptors are important targets in the treatment of anxiety. The roles of each of these two receptors on the anxiogenic effects of EW as well as their potential interrelation are discussed. The contribution of other receptor systems to the modulation of these effects is reviewed. Additionally, males and females show very different levels of anxiety during EW and studies on the role of the HPA axis in mediating these effects are examined. Finally, potential directions for better treatments for EW are discussed. Drug Dev. Res. 54:95-115, 2001.

Activation of Adenosine A1 Receptors Reduces Anxiety-Like Behavior During Acute Ethanol Withdrawal (Hangover) in Mice

“…On the other hand, alcoholism and alcohol abuse often involve heavy bouts of binge-like drinking interspersed with periods of abstinence, while some signs of withdrawal (such as fatigue, tremor, anxiety and depression) may be observed even after acute ingestion of substantial amounts of alcoholFa phenomenon commonly referred to as acute ethanol withdrawal or hangover (Smith and Barnes, 1983;Bogin et al, 1986;Wiese et al, 2000). Although many studies have consistently demonstrated increases in anxiety-like behavior during the withdrawal period after chronic exposure to ethanol in rodents (File et al, 1991(File et al, , 1993Lal et al, 1991;Knapp et al, 1993;Gatch et al, 1999;Gatch and Lal, 2001), there are limited experimental findings regarding this symptom after a single ethanol challenge dose.…”

“…Models of ethanol withdrawal in adult rodents have consistently demonstrated increases in anxiety-like behavior during the withdrawal period after chronic exposure to ethanol (File et al, 1991(File et al, , 1993Lal et al, 1991;Knapp et al, 1993;Gatch et al, 1999;Gatch and Lal, 2001). In contrast, few studies have examined the presence of withdrawal symptoms following a single dose of ethanol in rodents.…”

Ethanol Interference on Adenosine System

“…Although many studies have consistently demonstrated increases in anxiety-like behavior during the withdrawal period after chronic exposure to ethanol in rodents (Lal et al, 1991;Knapp et al, 1993;Gatch & Lal, 2001), there are limited experimental findings regarding this symptom after a single ethanol challenge dose. Prediger et al (2006) designed an experimental study of acute ethanol withdrawal (hangover) in mice, in which a timedependent development of anxiety-like behavior after an intraperitoneal administration of a single dose of ethanol (4 g/kg) in mice was assessed, and the potential of adenosine A 1 and A 2A receptor agonists in reducing this behavior was evaluated.…”

Behavioral and biochemical effects of ethanol withdrawal in zebrafish

“…It makes sense, then, that the majority of animal models of EtOH withdrawal are focused on anxiety-like behavior, with consistent effects observed in rodent models such as the elevated plus-maze, light/dark box, social interaction test, and a drug discrimination assay using pentylenetetrazole (Gatch & Lal, 2001). …”

“…In more serious conditions, patients presenting this EtOH withdrawal syndrome can present perceptive changes, agitation, mental confusion, significant increases in autonomic arousal, and seizures (Gatch & Lal, 2001;Krystal & Tabakoff, 2002). The most serious condition involves delirium tremens and death by hyperthermia, cardiac arrhythmia, and complications from withdrawal-induced seizures (Longo & Schuckit, 2014).…”