BIDIRECTIONAL SELECTIVE BREEDING FOR ETHANOL EFFECTS ON LOCOMOTOR-ACTIVITY - CHARACTERIZATION OF FAST AND SLOW MICE THROUGH SELECTION GENERATION-35

Increased recognition of the advantages of genetic animal models has l ed to heightened interest in their use acid development. A replicated bidirectional selective breeding project has produced lines of mice th at differ in their locomotor responses to 2.0 g/kg ethanol, FAST-1 and FAST-2 mice are highly stimulated by ethanol (EtOH), whereas SLOW-1 a nd SLOW-2 mice are either not affected or respond with locomotor depre ssion, Current heritability estimates indicate that similar to 6-8% of the response variance in the FAST lines and 2-10% of the response var iance in the SLOW lines is of additive genetic origin. Little systemat ic response to selection has occurred in recent generations, which imp lies that the limits of selection have been reached, Analysis of salin e activity over 35 generations of selection indicates that baseline ac tivities have not changed during the course of selection in three of t he lines, whereas baseline activity of FAST-1 mice has increased sligh tly, In EtOH dose-response studies (0.5-3.0 g/kg), FAST mice had bipha sic dose-response curves, whereas the locomotor activity of SLOW mice was either unaffected or depressed by all doses of EtOH. In addition, FAST mice spent more time in motion, traveled farther per movement, tr aversed greater distances in the center of the test chamber, and ambul ated more quickly than SLOW mice when given EtOH. FAST and SLOW mice d iffered in EtOH clearance rates; however, the differences were slight relative to the large difference in locomotor response, We encourage t he use of FAST and SLOW mice to investigate neurophysiological factors underlying sensitivity to the behavioral effects of EtOH, with a view to further testing of the postulated homology between locomotor stimu lant effects and addiction potential of drugs of abuse.