Effects of antidepressants on the performance in the forced swim test of two psychogenetically selected lines of rats that differ in coping strategies to aversive conditions

Introduction The selective breeding of Roman low-avoidance (RLA) and high-avoidance (RHA) rats for, respectively, poor versus rapid acquisition of active avoidance in a shuttle-box has produced two phenotypes that differ drastically in the reactivity to stressful stimuli: in tests used to assess emotionality, RLA rats display passive (“reactive”) coping and robust hypothalamus–pituitary–adrenal (HPA) axis reactivity, whereas RHA rats show proactive coping and blunted HPA axis responses. The behavioral and neuroendocrine traits that distinguish these lines suggest that RLA rats may be prone, whereas RHA rats may be resistant to develop depression-like behavior when exposed to stressful experimental conditions. Objective and methods To evaluate the performance of the Roman lines in the forced swim test, immobility, climbing, and swimming were assessed under baseline conditions (i.e., pretest in naïve animals or test after the administration of vehicle), and after subacute treatment with desipramine, fluoxetine, and chlorimipramine. Results Under baseline conditions, RLA rats displayed greater immobility and fewer climbing counts than RHA rats. In RLA rats, desipramine, fluoxetine, and chlorimipramine decreased immobility; moreover, desipramine and chlorimipramine increased climbing, whereas fluoxetine increased swimming. In RHA rats, none of these drugs affected immobility, swimming, or climbing. Conclusions RLA and RHA rats represent two divergent phenotypes respectively susceptible and resistant to display depression-like behavior in the forced swim test. Hence, comparative studies in these lines may help to develop novel working hypotheses on the relationships among genotype, temperament traits, and neural mechanisms underlying the vulnerability or resistance to stress-induced depression in humans.