Sensitivity to the effects of pharmacologically selective antidepressants in different strains of mice

Rationale: Recent advances in neurobehavioral genetics have increased the importance of research on the behavioral patterns of different mouse strains. A comprehensive comparison of inbred and outbred mouse strains was conducted to provide information on the range of performance and pharmacological effects in the forced swimming test, a behavioral test commonly used to measure the effects of antidepressant drugs. Objectives: Baseline performance and pharmacological responses to desipramine, a selective norepinephrine reuptake inhibitor, and fluoxetine, a selective serotonin reuptake inhibitor, were compared in seven inbred and four outbred mouse strains in the forced swimming test. Methods: Swim sessions were conducted by placing mice in individual glass cylinders filled with water for 6 min. The duration of behavioral immobility during the last 4 min of the test was scored from videotapes. Results: A 10-fold range of immobility values and coefficient of variation supported the existence of substantial behavioral differences between mouse strains in baseline performance in the FST. In general, inbred strains demonstrated lower variability than outbred strains. Desipramine dose-dependently reduced immobility in seven of the 11 strains tested, with DBA/2J and the C57BL/6J mice showing greater sensitivity than the other strains. In contrast, fluoxetine reduced immobility in only three out of the 11 strains tested, DBA/2J, BALB/cJ and NIH Swiss mice. Conclusions: Background strain is a critical variable in determining baseline performance and the sensitivity to different types of antidepressant drugs in the mouse FST. The use of such mouse strains may provide information on the genetic basis for strain differences in depressive behavior and differential sensitivity to diverse classes of antidepressants.