Animal models of clinical depression have frequently focused on the contribution of stressors to the induction of behavioral impairments and pharmacological intervention in the amelioration of these disturbances. Stressors provoke various behavioral disturbances and influence the activity of central neurotransmitters implicated in depression. It is our contention that those variables which favor the provocation of amine depletions or prevent the development of a neurochemical adaptation will increase vulnerability to behavioral disturbances. It is essential to consider, however, that marked interindividual and interstrain differences exist in the behavioral and neurochemical response to stressors, and in the effectiveness of antidepressant treatments.