Co-administration of amphetamine with alcohol results in decreased alcohol withdrawal severity in adolescent rats

Abstract

Simultaneous use of stimulants and alcohol is a growing problem, particularly among older adolescents already prone to binge alcohol consumption. Adolescent rats consume high levels of alcohol when administered in a liquid diet and develop a strong alcohol withdrawal syndrome. We exploited this system to administer amphetamine in combination with alcohol and to test the effect of co-administration of amphetamine on alcohol withdrawal-induced hypoactivity and overall withdrawal severity. The presence of dietary amphetamine (≤40 mg/l) had no effect on consumption of control or alcohol-containing diets. Measured in an activity chamber, alcohol withdrawal hypoactivity was reduced significantly by co-administration of amphetamine with alcohol. Overall withdrawal severity was also reduced significantly when rats consumed amphetamine with alcohol. The results suggest that amphetamine co-use may mask physical signs of alcohol dependency and add to the importance of educational strategies pointing out the potential problems associated with co-use of stimulants and alcohol.

Sequential Changes in Brain Glutamate and Adenosine A1 Receptors May Explain Severity of Adolescent Alcohol Withdrawal after Consumption of High Levels of Alcohol

“…Alcohol-containing liquid diets provided an approach leading to high levels of alcohol consumption by adolescent rats and progressively severe withdrawal symptoms over time. Alcohol consumption and severity of withdrawal reported here are consistent with our previous reports using Long-Evans adolescents and liquid diets as the source of alcohol [15, 17–19]. It is important to note that the interruptions to the alcohol administration schedule in this study to allow for withdrawal measures at 4 and 11 days had no significant impact on the final withdrawal severity compared to our previous reports with continuous uninterrupted alcohol administration for the entire period.…”

“…In studies of chronic alcohol consumption, rats were housed individually and fed a preformulated liquid diet [26] (LD'82 Liquidiet, Bioserv Inc., Frenchtown, NJ). At a final concentration of 3.5% (w/v), ethanol was administered in the liquid diet beginning at postnatal day 28 (P28) and continuing up to 18 days as described previously [15, 18, 19]. This coincides with a starting point in early adolescence for rats [8].…”

“…Based on previous work [15, 18, 19], rats were evaluated for severity of ethanol withdrawal beginning at 6 hours after being switched from the ethanol-containing diet to a control formula (no ethanol) liquid diet (Bioserv Inc.) or simply to regular rat chow and tap water to affect ethanol withdrawal. Based on the characterization of the alcohol withdrawal syndrome in adult rats by Majchrowicz [27], the scoring system of Penland et al [28] was used to assess the severity of withdrawal symptoms as described previously [18, 19]. This is a 4-point scale, including scores of 1.0 for general hyperactivity, 2.0 for caudal region tremors, 3.0 for head tremors, 3.2 for induced running episodes, and 3.8 for convulsions during withdrawal.…”

“…When given alcohol as part of a liquid diet, adolescent rats consume high levels of alcohol, achieve blood alcohol concentrations well above the threshold for binge drinking among human adolescents, and develop a severe alcohol withdrawal syndrome [15–19]. The latter is marked by a high percentage of convulsive episodes during the withdrawal period.…”

“…In addition, liquid diets can be exploited to study coadministration of other drugs with alcohol. We have used this system to show that administration of alcohol with either caffeine [18] or amphetamine [19] decreased the severity of subsequent alcohol withdrawal. This adds to the importance of understanding biochemical changes occurring during chronic alcohol consumption.…”