The effect of chronic treatment with imipramine on the responsiveness of hippocampal CA1 neurons to phenylephrine and serotonin in a chronic mild stress model of depression

Abstract

The effect of chronic mild stress (CMS) and chronic treatment with the tricyclic antidepressant drug imipramine (10 mg/kg/day for 5 weeks) on neuronal responsiveness to the α 1-noradrenergic agonist phenylephrine and serotonin (5-HT) was examined ex vivo, in the CA1 cell layer of the rat hippocampal slice preparation. We corroborated some previous findings that CMS, which had been used as an animal model of depression, decreased the consumption of a 1% sucrose solution and that that effect was reversed by chronic administration of imipramine. Imipramine did not change the sucrose consumption in control animals. In both control and stressed animals, phenylephrine (5 μ M) and 5-HT (10 μ M) attenuated the amplitude of the population spikes evoked in the CAI pyramidal cell layer by stimulation of Schaffer collateral/commissural fibers. Those inhibitory effects of phenylephrine and 5-HT were significantly potentiated by chronic treatment with imipramine. The imipramine-induced potentiation was similar in slices from control and stressed animals. These results suggest that the imipramine-induced functional changes in α 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.