Chronic effects of imipramine and lithium on postsynaptic 5-HT1A and 5-HT1B sites and on presynaptic 5-HT3 sites in rat brain.
The effects of chronic treatment with imipramine, a tricyclic antidepressant, or lithium, an antimanic-depressive illness drug, on postsynaptic serotonin-1A (5-HT1A) and 5-HT1B 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 (Bmax) for postsynaptic 5-HT1A 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 Bmax for postsynaptic 5-HT1B and presynaptic 5-HT3 in either the frontal cortex or the hippocampus. Chronic i.p. administration (21 days) of lithium reduced the Bmax for postsynaptic 5-HT1A 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-HT1A 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 tob e related to the down-regulation of postsynaptic 5-HT1A receptors in addition to postsynaptic 5-HT2 receptors, which may also have an important role in the antidepressant effects of these drugs.
Mizuta
T
T
Department of Pharmacology, Hiroshima University School of Medicine, Japan.
Segawa
T
T
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects; D007099:Imipramine / Q000008:administration & dosage / Q000494:pharmacology*; D008094:Lithium / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects*
D011985:Receptors, Serotonin; D008094:Lithium; D007099:Imipramine