Selective breeding of rats for differences in reactivity to alcohol. An approach to an animal model of alcoholism. I. General procedures.

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Abstract
A breeding program was described whose purpose was to develop a strain of rats in which the injection of a standard dose of alcohol will result in objectively measurable intoxication and another strain in which the same dose will result in virtually no effect. The foundation stock consisted of 16 Sprague-Dawley albino and 16 Long-Evans hooded rats, 8 males and 8 females of each strain. The rats were tested in 2 replications in a 4 .times. 4 Latin-square design balanced for sex, strain and alcohol dose. Activity level was tested at 7-day intervals. After a 24-h fast each rat received an i.p. injection of placebo or 0.75, 1.5 or 2.25 g of alcohol/kg of body wt (5, 10 or 15% wt/vol solutions in saline) and was placed in an activity chamber for 75 min. Over-all activity decreased monotonically with increasing dose of alcohol, although the greatest decrement between 2 successive doses occurred between 0.75 and 1.50 g/kg. Individual variation in response to the same dose of alcohol was great: at 2.25 g/kg the range in activity scores 16-30 min after the injection were 30-842 in the 1st replication and 30-251 in the 2nd replication, even though the mean blood alcohol concentrations (BAC) were similar (0.25 and 0.24%, respectively). In succeeding generations activity was measured after saline and after 1.5 g of alcohol/kg. In each generation 38-78 rats (aged 56-70 days) were tested. Those whose motor activity was most affected (MA) and least affected (LA) by alcohol were chosen for breeding on the basis of the ratio of activity after alcohol to that after saline during the 16-30 min after injection. By the 5th generation the 2 strains were distinct in their reaction to alcohol, mostly due to a decrease in the alcohol: saline ratio in the MA group rather than an increase in the LA group. By the 9th generation mean activity scores in the MA and LA strains 16-30 min after the saline injection were 692.8 and 646.5, and after alcohol, 84.5 and 337.9. The mean BACS 40 min after the injection were 0.18% in both strains. The breeding program promises to provide 2 strains of rats with homogeneous responses to the effects of alcohol for use in developing an animal model of [human] alcoholism.