PHENOBARBITAL SENSITIVITY IN HAS AND LAS RATS BEFORE AND AFTER CHRONIC ADMINISTRATION OF ETHANOL

Rats selectively bred for high alcohol sensitivity (HAS) or low alcoho l sensitivity (LAS) were tested for initial sensitivity to hypnotic do ses of ethanol and a locomotor-altering dose of phenobarbital. Followi ng 6 weeks of either a pair-fed control or 33% ethanol-derived calorie diet, animals were tested again for tolerance to ethanol and cross-to lerance to phenobarbital. HAS and LAS rats did not differ in baseline open field or Rotarod activity before chronic ethanol treatment. Howev er, HAS rats were more sensitive to 50 mg/kg phenobarbital relative to LAS rats. Both control- and ethanol-diet rats appeared to be less sen sitive to phenobarbital after the 6-week treatment period. Chronic eth anol-exposed HAS and LAS rats demonstrated tolerance to ethanol and cr oss-tolerance to phenobarbital, and in particular LAS rats were even m ore active in the open field following phenobarbital relative to contr ols. In summary, significant differences in response to phenobarbital were observed between HAS and LAS rats. These observations suggest tha t initial sensitivity and tolerance to ethanol are associated with dif ferences in phenobarbital sensitivity and are influenced by similar ge nes. (C) 1997 Elsevier Science Inc.