IMIPRAMINE AND FLUOXETINE PREVENT THE STRESS-INDUCED ESCAPE DEFICITS IN RATS THROUGH A DISTINCT MECHANISM OF ACTION

A large body of evidence indicates that brain monoamines are involved in the pathogenesis of mental depression, as well as in the mechanism of action of most antidepressant treatments. The present report shows that long-term exposure to imipramine (IMI) or fluoxetine (FLX) was eq ually potent in preventing the escape deficits produced in rats by rep eated unavoidable shocks. The acute administration of SCH 23390, a sel ective D1 dopamine receptor blocker, shortly before the inescapable sh ock session, entirely prevented IMI effect on escape performance, but only partially prevented that of FLX. Moreover, pindolol (an antagonis t of beta-adrenoceptors and of serotonin 5-HT1A and 5-HT1B receptors) completely antagonized the efficacy of FLX in preventing escape defici ts, whereas it did not affect the activity of IMI. The acute administr ation of propranolol failed to alter the effect of either antidepressa nt. It was concluded that in rats, the efficacy of IMI in counteractin g the stress-induced behavioral sequelae is mainly mediated by the act ivation of D1 dopamine receptors, whereas that of FLX is largely depen dent upon the stimulation of post-synaptic 5-HT1A receptors. Finally, the effects of the two drugs appear to be totally unrelated to activat ion of beta-adrenoceptors.