Alcohol dependence induced in rats by semivoluntary intermittent intake

Abstract

The objective of the present experiment was to assess ethyl alcohol (ETOH) dependence brought about by a semivoluntary intermittent intake regimen in rats. Male Wistar rats weighing 150-250 g at the onset of the experiment were assigned to the following groups: 0% ETOH (N = 11), 5% ETOH (N = 20), 20% ETOH (N = 20) and 40% ETOH (N = 18). ETOH solutions were offered at the end of the day and overnight from Monday to Friday, and throughout weekends, for 90 days. The concentration of the ETOH solutions was increased in a stepwise fashion allowing the rats to get used to the taste of alcohol. Reposition of pure water was permitted during 1-h water drinking periods in the morning. Daily volume intake (± SEM) averaged 25.4 ± 0.4 ml (0% ETOH), 23.8 ± 0.6 ml (5% ETOH), 17.6 ± 0.7 ml (20% ETOH) and 17.5 ± 0.6 ml (40% ETOH). ETOH consumption differed significantly (P<0.05) among groups, averaging 4.4 ± 0.2 g kg -1 day -1 (5% ETOH), 10.3 ± 0.3 g kg -1 day -1 (20% ETOH) and 26 ± 1.2 g kg -1 day -1 (40% ETOH). Furthermore, ETOH detection in plasma 10-12 h after offering the solution indicated that its consumption in the 40% ETOH group was sufficient to override its metabolism. Overt signs of ETOH dependence, such as increased thirst, hyperactivity, puffing, hair ruffling and startle responsiveness as well as reduced drowsiness, were significantly increased in the 20% and 40% ETOH groups compared to the 0% and 5% groups. Accordingly, the model described here proved to be a useful tool for the evaluation of subtle or moderate behavioral and physical consequences of long-term ETOH intake. Key wordsExperimental dependence on ethyl alcohol (ETOH) is usually induced by 3 methods of drug administration: involuntary, semivoluntary or voluntary (1). While the involuntary method refers to the forced drug administration by gastric intubation or by the intravenous, intraperitoneal and pulmonary routes (2), in the semivoluntary method ETOH is offered as part of a liquid or food diet, which is ingested spontaneously (3), and in the voluntary method the animals have to learn to self-administer the drug (4). Both advantages and disadvantages have been observed for each procedure. Thus, whereas the involuntary method is quite suitable for the evaluation of the development of tolerance and early signs of physical dependence (1,5), the procedure is rather ag-

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