Imipramine and fluoxetine prevent the stress-induced escape deficit 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 equally potent in preventing the escape deficits produced in rats by repeated unavoidable shocks. The acute administration of SCH 23390, a selective D1 dopamine receptor blocker, shortly before the inescapable shock session, entirely prevented IMI effect on escape performance, but only partially prevented that of FLX. Moreover, pindolol (an antagonist of beta-adrenoceptors and of serotonin 5-HT(1A) and 5-HT(1B) receptors) completely antagonized the efficacy of FLX in preventing escape deficits, whereas it did not effect the activity of IMI. The acute administration of propranolol failed to alter the effect of either antidepressant. It was concluded that in rats, the efficacy of IMI in counteracting the stress-induced behavioral sequelae is mainly mediated by the activation of D1 dopamine receptors, whereas that of FLX is largely dependent upon the stimulation of post-synaptic 5-HT(1A) receptors. Finally, the effects of the two drugs appear to be totally unrelated to activation of beta-adrenoceptors.