Chronic Effects of Imipramine and Lithium on Postsynaptic 5-HT_1A and 5-HT_1B Sites and on Presynaptic 5-HT₃ Sites in Rat Brain

Abstract

The effects of chronic treatment with imipramine, a tricyclic antidepressant, or lithium, an antimanic-depressive illness drug, on postsynaptic serotonin-1A (5-HT_1A) and 5-HT_1B sites and on presynaptic 5-HT₃ sites in the frontal cortex and hippocampus from rat brains were studied. Chronic i.p. administration (21 days) of imipramine reduced the maximum number of binding sites (B_max) for postsynaptic 5-HT_1A as monitored by the radioligands ³H-5-HT or ³H-8-hydroxy-2-(di-n-propylamino)tetralin (³H-8-OH-DPAT), but did not change the B_max for postsynaptic 5-HT_1B and presynaptic 5-HT₃ in either the frontal cortex or the hippocampus. Chronic i.p. administration (21 days) of lithium reduced the B_max for postsynaptic 5-HT_1A sites in the hippocampus, but not in the frontal cortex. There was a specific difference between imipramine and lithium regarding the inhibitory effect on postsynaptic 5-HT_1A sites in the frontal cortex. In addition, lithium decreased the affinity of presynaptic 5-HT₃ sites in the hippocampus. These findings may be also consistent with the inhibitory effect of lithium on presynaptic autoreceptors, which results in an increase of 5-HT release. It is concluded that enhanced 5-HT neurotransmission which develops during chronic treatment with imipramine or lithium seems to be related to the down-regulation of postsynaptic 5-HT_1A receptors in addition to postsynaptic 5-HT₂ receptors, which may also have an important role in the antidepressant effects of these drugs.