Dark Agouti and Fischer 344 rats: Differential behavioral responses to morphine and biochemical differences in the ventral tegmental area

We sought to identify behavioral and biochemical differences between Dark A gouti and Fischer 344 inbred rat strains to assess whether they could serve as a model of genetically determined differences in sensitivity to drugs o f abuse. We compared the strains for the following traits: morphine-induced locomotor activity and sensitization; circadian variation in plasma levels of corticosterone, a hormone reported to affect sensitivity to drugs of ab use; and several biochemical parameters in the ventral tegmental area and n ucleus accumbens, brain regions implicated in the locomotor activating and reinforcing actions of drugs of abuse. Fischer 344 rats exhibited greater i nitial locomotor responses to morphine but, unlike Dark Agouti rats, did no t develop sensitization to a second morphine exposure. Fischer 344 rats dis played a marked rise in basal plasma corticosterone levels in the late ligh t phase and early dark phase, whereas Dark Agouti rats showed no significan t circadian variation in corticosterone levels. Relative to drug-naive Fisc her 344 rats, drug-naive Dark Agouti rats showed higher levels of tyrosine hydroxylase and glial fibrillary acidic protein, and lower levels of neurof ilament proteins, in the ventral tegmental area. In contrast, no strain dif ferences were found in levels of tyrosine hydroxylase, specific G protein s ubunits or protein kinase A in the nucleus accumbens. Together, these results demonstrate that Dark Agouti rats and Fischer 344 r ats exhibit differences in specific behavioral, endocrine and biochemical p arameters related to sensitivity to drugs of abuse. (C) 1998 IBRO. Publishe d by Elsevier Science Ltd.