STRESS AND ANTIDEPRESSANT EFFECTS ON HIPPOCAMPAL AND CORTICAL 5-HT(1A) AND 5-HT(2) RECEPTORS AND TRANSPORT SITES FOR SEROTONIN

The interactions between 14 days of repeated restraint stress and dail y administration of imipramine or tianeptine (2 h before the beginning of stress) were investigated in rats to assess responses of 5-HT2 and 5-HT1A receptors and serotonin transporter sites labelled by [H-3]par oxetine in the cerebral cortex and hippocampus, two brain regions in w hich adrenal steroid effects on serotonin receptor-binding have been r eported. 5-HT2 sites, labelled by [I-125]7-amino-8-iodo ketanserin, we re decreased in parietal cerebral cortex layers 3 and 5 by imipramine treatment, but not by tianeptine treatment and not by daily restraint stress. Stress, but not antidepressant, depressed 5-HT1A sites labelle d with [H-3]8-hydroxy-DPAT in hippocampal fields CA3, CA4 and dentate gyrus. [H-3]paroxetine-binding to serotonin transporter sites was decr eased by tianeptine treatment as well as by imipramine in both hippoca mpus and cerebral cortex, with some overlap of the fields that were si gnificantly affected, whereas there were no effects of stress per se a nd no evidence of a stress x drug interaction. These results are discu ssed in relation to similarities and differences in the effects of dif ferent antidepressant drugs on the serotonergic system of the rat brai n. Whereas the actions of imipramine and tianeptine on 5-HT2 and 5-HT1 A receptors are specific to each drug, the surprising finding of a sim ilar effect of both drugs to reduce serotonin transporter sites labell ed by [H-3]paroxetine suggest the possibility of a common action for t hese two drugs in spite of their opposite effects on serotonin re-upta ke.