Effects of triiodothyronine and imipramine on basal 5-HT levels and 5-HT(1) autoreceptor activity in rat cortex.
Clinical studies have shown that triiodothyronine (T3) both augments and accelerates the therapeutic response to antidepressant drugs, particularly tricyclics. There is evidence that this effect is mediated by the serotonergic system. We show here that T3 administered daily for 7 days over the range 0.02-0.5 mg/kg increases basal serotonin (5-hydroxytryptamine, 5-HT) levels, as measured by in vivo microdialysis in rat cortex, in a dose-dependent fashion. All the doses of T3 examined reduced 5-HT(1A) autoreceptor activity, as measured by the effect of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 0.05 mg/kg s.c.) to decrease 5-HT levels in frontal cortex. T3 administered daily for 14 days at 0.02 mg/kg also reduced 5-HT(1B) autoreceptor activity, as measured by the effect of locally administered 3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one (CP 93129, 10 microM) to decrease 5-HT levels. In animals administered imipramine (10 mg/kg/day by osmotic minipump) concurrently with T3 injections, no further changes in either 5-HT(1A) or 5-HT(1B) autoreceptor activity were seen. We suggest that the effect of T3 to accelerate the therapeutic actions of antidepressant drugs may be due to a combination of the actions of T3 at autoreceptors and the actions of the drugs at postsynaptic 5-HT(1A) receptors.
Gur
Eitan
E
Department of Psychiatry, Hadassah-Hebrew University Medical Center, POB 12000, Jerusalem 91120, Israel.
Lifschytz
Tsuri
T
Lerer
Bernard
B
Newman
Michael E
ME
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D017660:Autoreceptors / Q000187:drug effects* / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007099:Imipramine / Q000494:pharmacology*; D008297:Male; D051381:Rats; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D014284:Triiodothyronine / Q000494:pharmacology*
D000929:Antidepressive Agents, Tricyclic; D017660:Autoreceptors; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D014284:Triiodothyronine; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D007099:Imipramine