Rats selectively bred for high alcohol sensitivity (HAS) or low alcohol sensitivity (LAS) were tested for initial sensitivity to hypnotic doses of ethanol and a locomotor-altering dose of phenobarbital. Following 6 weeks of either a pair-fed control or 33% ethanol-derived calorie diet, animals were tested again for tolerance to ethanol and cross-tolerance to phenobarbital. HAS and LAS rats did not differ in baseline open field or Rotarod activity before chronic ethanol treatment. However, HAS rats were more sensitive to 50 mg/ kg phenobarbital relative to LAS rats. Both control- and ethanol-diet rats appeared to be less sensitive to phenobarbital after the 6-week treatment period. Chronic ethanol-exposed HAS and LAS rats demonstrated tolerance to ethanol and cross-tolerance to phenobarbital, and in particular LAS rats were even more active in the open field following phenobarbital relative to controls. In summary, significant differences in response to phenobarbital were observed between HAS and LAS rats. These observations suggest that initial sensitivity and tolerance to ethanol are associated with differences in phenobarbital sensitivity and are influenced by similar genes.
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