Genetic selections for nicotine and cocaine sensitivity in mice.

We are using selective breeding to develop lines of mice which differ maximally in their responses to nicotine, and independent lines of mice which differ maximally in their responses to cocaine. The foundation population was the genetically heterogeneous HS mice. On day 1, baseline (saline injected) activity of each mouse was measured in an automated Y-maze over 3 minutes. On day 2, animals were tested for sensitivity to nicotine (0.75 mg/kg) in the same apparatus. A residual score, calculated from the regression of nicotine scores on saline scores for the whole population, was calculated for each animal. The most severely affected mice (lowest residual scores) were mated to form duplicate Nicotine-Depressed lines; the most stimulated mice (highest residual scores) were mated to form duplicate Nicotine-Activated lines. A random sampling of individuals was chosen without regard to residual scores for production of duplicate Control lines. Duplicate lines of mice activated and depressed by cocaine are being produced in an analogous fashion using 50 mg/kg cocaine as the test dose. Successful selective breeding for a drug-related trait provides clear evidence of a heritable component for that trait. These selected lines of mice will ultimately be used to study hypotheses involving genetic control of response to these drugs.