Observations of novel behaviors as indices of ethanol withdrawal-induced anxiety.

One of the prominent symptoms in alcoholics during withdrawal is an intense feeling of anxiety. Recently new tests have become available which may index anxiety in rodents. We have evaluated two such tests in our model of withdrawal from ethanol (ET) in rats. Rats were given either ET in milk (7-13 g/kg/4 days) or equicaloric dextrin maltose in milk via implanted gastric cannuli. Rats were scored for classical withdrawal symptoms (tremors, convulsions, stereotyped behavior), for stimulus-elicited ultrasonic vocalizations (USVs), and in one study for exploration of novel objects placed in their home cage at various points after the last dose of ET. In Sprague-Dawley rats, classical withdrawal symptoms were highest between 8-12 hours, and disappeared by 36 hours. Latency to explore a novel object was unchanged, but duration was depressed between 10-30 hours, and was recovered by 70 hours. Following a less intense Day 1 treatment regimen in Long-Evans rats, the vocalizations were greatly increased in number, and peak response occurred sooner (6 hours post-infusion) and was of shorter overall duration (50 hours). Pretreatment with diazepam (1.25-5.0 mg/kg) depressed the number of vocalizations during ET withdrawal (ETW), which suggests that this measure could index anxiety in animal models of withdrawal from ET.