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Technique for producing an alcohol withdrawal syndrome in rats
550
EBBS ABSTRACTS
Technique for producing an alcohol wilhdrawal syndrome in rats ResearchLaboratories of the Finnish State Alcohol Monopoly (Alko), Helsinki (Finland) HENRIK WALLGREN, ANNA-LIISA KOSUNEN AND LIISA AHTEE - -
A barrier to study the alcohol withdrawal illness has been the lack of an animal model. Recently, a withdrawal syndrome has been described in monkeys, dogs, and mice, and less severe symptoms in rats. We have developed a technique by which the syndrome can be induced in rats. Tertiary butanol was chosen because it is slowly eliminated and facilitates maintenance of intoxication. Although it is not oxidised to aldehyde, its pharmacological action is closely similar to that of ethanol. Male rats 5-6 months old were used, Alcohol was given by stomach tube twice daily for about 18 days in doses increasing from 1.5 g/kg/day initially to approximately 3 g/kg/day by the end of treatment, taking care that intoxication was maintained. Constipation caused by dry lab chow was avoided by the use of a liquid diet. Eleven groups of 8-15 rats, housed one to a cage, were used in succession. Loss of animals during alcohol administration was brought down to about 3 animals per group. After termination of treatment, severe symptoms of autonomic and central excitation developed. In 20-50 % of the survivors of each group, convulsions occasionally terminating in death were observed. The symptoms lasted for about two days. Recovery appeared to be complete. Three groups of animals treated with ethanol (6-12 g/kg/day) showed similar withdrawal symptoms. Brain 5-HT, 5-HIAA, and noradrenaline (NA) were determined at the end of ethanol treatment both in intoxication and withdrawal. Neither 5-HT nor NA content was changed. 5-HIAA tended to increase in intoxication and withdrawal, and NA increased in intoxication. The similarity of the withdrawal state after butanol and after ethanol shows that conversion of alcohol to aldehyde is not important for development of the withdrawal symptoms. The technique seems promising but quantification of the symptoms presents difficulties.
The effects of drugs and s e l f - ~
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GORAN WAHLSTR6M- - Department of Pharmacology, University of Uppsala, Uppsala
(Sweden) The self-selected circadian rhythm of light and darkness was recorded in the canary. The canaries are kept singly. Each cage has a soparate light source and this light can be regulated by the bird. The light is extinguished as long as the bird stays on one perch inside the cage (the 'night perch'). During normal conditions there is one period of light (activity) and one of darkness (res0 in each circadian period. With this method it is thus possible to pick out drugs which make the birds choose the night perch earlier than expected (roost early). There is no absolute identity between this behaviour and sleep induction but they are closely related. Brain Research, 42 (1972) 535-553
EBBS ABSTRACTS
Technique for producing an alcohol wilhdrawal syndrome in rats ResearchLaboratories of the Finnish State Alcohol Monopoly (Alko), Helsinki (Finland) HENRIK WALLGREN, ANNA-LIISA KOSUNEN AND LIISA AHTEE - -
A barrier to study the alcohol withdrawal illness has been the lack of an animal model. Recently, a withdrawal syndrome has been described in monkeys, dogs, and mice, and less severe symptoms in rats. We have developed a technique by which the syndrome can be induced in rats. Tertiary butanol was chosen because it is slowly eliminated and facilitates maintenance of intoxication. Although it is not oxidised to aldehyde, its pharmacological action is closely similar to that of ethanol. Male rats 5-6 months old were used, Alcohol was given by stomach tube twice daily for about 18 days in doses increasing from 1.5 g/kg/day initially to approximately 3 g/kg/day by the end of treatment, taking care that intoxication was maintained. Constipation caused by dry lab chow was avoided by the use of a liquid diet. Eleven groups of 8-15 rats, housed one to a cage, were used in succession. Loss of animals during alcohol administration was brought down to about 3 animals per group. After termination of treatment, severe symptoms of autonomic and central excitation developed. In 20-50 % of the survivors of each group, convulsions occasionally terminating in death were observed. The symptoms lasted for about two days. Recovery appeared to be complete. Three groups of animals treated with ethanol (6-12 g/kg/day) showed similar withdrawal symptoms. Brain 5-HT, 5-HIAA, and noradrenaline (NA) were determined at the end of ethanol treatment both in intoxication and withdrawal. Neither 5-HT nor NA content was changed. 5-HIAA tended to increase in intoxication and withdrawal, and NA increased in intoxication. The similarity of the withdrawal state after butanol and after ethanol shows that conversion of alcohol to aldehyde is not important for development of the withdrawal symptoms. The technique seems promising but quantification of the symptoms presents difficulties.
The effects of drugs and s e l f - ~
~
~
~
of ~:,.~mm~/
GORAN WAHLSTR6M- - Department of Pharmacology, University of Uppsala, Uppsala
(Sweden) The self-selected circadian rhythm of light and darkness was recorded in the canary. The canaries are kept singly. Each cage has a soparate light source and this light can be regulated by the bird. The light is extinguished as long as the bird stays on one perch inside the cage (the 'night perch'). During normal conditions there is one period of light (activity) and one of darkness (res0 in each circadian period. With this method it is thus possible to pick out drugs which make the birds choose the night perch earlier than expected (roost early). There is no absolute identity between this behaviour and sleep induction but they are closely related. Brain Research, 42 (1972) 535-553