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Filippo Drago STRESS, STRESS MODULATORS AND DEPRESSION

Abstract :


I
t is now widely accepted that stress and depression are closely interrelated and inter-depended. Moreover, the issue «when the stress is finishing and when the depression is starting», is difficult to clarify. In pre-clinical studies, an important issue is represented by the manipulation of animals during experimental procedure as source of stress. Although the model of forced swim test (FST) is widely accepted to predict antidepressant activity of a drug, it should be corrected in order to avoid manipulation induced stress. In recent experiments, male and female rats of the Wistar strain were injected with clomipramine (50 mg/kg, i.p.) or saline. A group of animals also received electric shocks of different intensity and duration 24, 5 and 1 h before being subjected to forced swim test. Application of mild shocks (5 ms, 0.1 mA) significantly reduced immobility time in forced swim test of untreated male rats and augmented clomipramine effect on this parameter.

Moderate shocks of higher intensity or duration (5 ms, 1.0 mA) also resulted in decreased immobility time of untreated male rats, but in reduced effect of clomipramine treatment. Furthermore, application of severe shocks (10 ms, 1.0 mA) increased the immobility time in untreated animals and totally abolished clomipramine effect in forced swim test. Untreated non-shocked female rats in proestrous and estrous phases exhibited a longer immobility time as compared to diestrous animals. Immobility time appeared to be generally higher when mild, moderate or severe shocks were applied prior to behavioral testing in proestrous and estrous animals, while the behavioral response of diestrous and metestrous animals did not differ from that of controls. Clomipramine effect on immobility time was generally reduced by application of shocks of every strength. Stress-induced plasma corticosterone levels surge correlated with intensity and duration of shocks in both male and female rats, but clomipramine treatment generally blunted the hormonal response. However, severe shocks were followed by a surge of plasma corticosterone levels in both male and female clomipramine-treated rats.
These results demonstrate that duration and intensity of stressful stimuli may deeply affect the behavioral response of rats in forced swim test and influence clomipramine effect in this behavioral model depending on gender-based variables, probably of the hormonal type. Among hormonal stress modulators, prolactin exerts clear protective effects against behavioral and physical changes induced by stress. This holds also for depressive behavior that may be reduced in hyperprolactinemic animals.

Angelo Contarino