Stress and antidepressant effects on hippocampal and cortical 5-HT1A and 5-HT2 receptors and transport sites for serotonin

The interactions between 14 days of repeated restraint stress and daily administration of imipramine or tianeptine (2 h before the beginning of stress) were investigated in rats to assess responses of 5-HT 2 and 5-HT 1A receptors and serotonin transporter sites labelled by [ 3 H]paraxotine in the cerebral cortex and hippopcampus, two brain regions in which adrenal steroid effects on serotonin receptor-binding have been reported. 5-HT 2 sites, labelled by [ 125 I]7-amino-8-iodo ketanserin, were decreased in parietal cerebral cortex layers 3 and 5 imipramine treatment, but not by tianeptine treatment and not by daily restraint stress. Stress, but not antidepressant, depressed 5-HT 1A sites labelled with [ 3 H]8-hydroxy-DPAT in hippocampal fields CA3, CA4 and dentate gyrus. [ 3 H]paroxetine-binding to serotinin transporter sites was decreased by tianeptine treatment as well as by imipramine in both hippocampus and cerebral cortex,with some overlap of the fields that were significantly affected, whereas there were no effects of stress per se and no evidence of a stress× drug interaction. These results are discussed in relation to similarities and differences in the effects of different antidepressant drugs on the serotonergic system of the rat brain. Wheras the actions of imipramine and tianeptine on 5-HT 2 and 5-HT 1A receptors are specific to each drug, the surprising finding of a similar effect of both drugs to reduce serotonin transporter sites labelled by [ 3 H]paroxetine suggest the possibility of a common action for these two drugs in spite of their opposite effects on serotonin re-uptake.