THE EFFECT OF CHRONIC TREATMENT WITH IMIPRAMINE ON THE RESPONSIVENESSOF HIPPOCAMPAL CA1 NEURONS TO PHENYLEPHRINE AND SEROTONIN IN A CHRONIC MILD STRESS MODEL OF DEPRESSION

The effect of chronic mild stress (CMS) and chronic treatment with the tricyclic antidepressant drug imipramine (10 mg/kg/day for 5 weeks) o n neuronal responsiveness to the alpha 1-noradrenergic agonist phenyle phrine and serotonin (5-HT) was examined ex vivo, in the CA1 cell laye r of the rat hippocampal slice preparation. We corroborated some previ ous findings that CMS, which had been used as an animal model of depre ssion, decreased the consumption of a 1% sucrose solution and that tha t effect was reversed by chronic administration of imipramine. Imipram ine did not change the sucrose consumption in control animals. In both control and stressed animals, phenylephrine (5 mu M) and 5-HT (10 mu M) attenuated the amplitude of the population spikes evoked in the CA1 pyramidal cell layer by stimulation of Schaffer collateral/commissura l fibers. Those inhibitory effects of phenylephrine and 5-HT were sign ificantly potentiated by chronic treatment with imipramine. The Imipra mine-induced potentiation was similar in slices from control and stres sed animals. These results suggest that the imipramine-induced functio nal changes in alpha 1-noradrenergic and serotonergic receptors in the hippocampus are not involved in the anti-anhedonic effect of chronic imipramine administration in the CMS model of depression.