| Abstrakt: |
Abstract While there is evidence that individual differences in response to cocaine are mediated, in part, by genetic factors, no single gene has been identified that can account for differential responsivity to cocaine. Recent studies in our laboratory may have moved us closer to identification of the gene(s) underlying cocaine sensitivity. We have identified several cocaine-related phenotypes on which two substrains of C57BL mice (6J and ByJ) differ. The genealogy of these two substrains leads to the expectation that they should be genetically very similar, differing at only a few loci. The large differences between the two substrains in cocaine sensitivity may be influenced by allelic differences at a major gene mediating the actions of cocaine. Naive By J mice are more resistant to cocaine-induced seizures than are 6J mice. Furthermore, among 6J mice repeated exposure to cocaine results in a decreased susceptibility to cocaine-induced seizure, while among By J mice, the same treatment gives rise to an increased susceptibility to seizures. In contrast to their lower sensitivity to cocaine-induced seizures, By J mice show a greater sensitivity to cocaine's locomotor stimulant effects. Furthermore, the repeated pairing of cocaine and the test environment results in the development of conditioned locomotion during subsequent exposure to thru environment among 6J, but not By J, mice. Similarly, a greater degree of conditioned sensitization to the locomotor stimulant effects of cocaine develops in 6J mice. [ABSTRACT FROM AUTHOR] |
