Chronic effects of imipramine and lithium on postsynaptic 5-HT1A and 5-HT1B sites and on presynaptic 5-HT3 sites in rat brain.
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The effects of chronic treatment with imipramine, a tricyclic antidepressant, or lithium, an antimanic-depressive illness drug, on postsynaptic serotonin-1A (5-HT<SUB>1A</SUB>) and 5-HT<SUB>1B</SUB> sites and on presynaptic 5-HT<SUB>3</SUB> 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<SUB>max</SUB>) for postsynaptic 5-HT<SUB>1A</SUB> as monitored by the radioligands <SUP>3</SUP>H-5-HT or <SUP>3</SUP>H-8-hydroxy-2-(di-n-propylamino)tetralin (<SUP>3</SUP>H-8-OH-DPAT), but did not change the B<SUB>max</SUB> for postsynaptic 5-HT<SUB>1B</SUB> and presynaptic 5-HT<SUB>3</SUB> in either the frontal cortex or the hippocampus. Chronic i.p. administration (21 days) of lithium reduced the B<SUB>max</SUB> for postsynaptic 5-HT<SUB>1A</SUB> 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<SUB>1A</SUB> sites in the frontal cortex. In addition, lithium decreased the affinity of presynaptic 5-HT<SUB>3</SUB> 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<SUB>1A</SUB> receptors in addition to postsynaptic 5-HT<SUB>2</SUB> receptors, which may also have an important role in the antidepressant effects of these drugs.
- 公益社団法人 日本薬理学会の論文