Effects of triiodothyronine on 5-HT(1A) and 5-HT(1B) autoreceptor activity, and postsynaptic 5-HT(1A) receptor activity, in rat hypothalamus: lack of interaction with imipramine.
Triiodothyronine (T3) is effective in both augmenting and accelerating the therapeutic response to antidepressant drugs, especially tricyclics, and there is evidence from both human and animal studies that it acts on serotonergic neurotransmission. In this work we examined the effects of T3 alone and together with imipramine on 5-HT levels in the hypothalamus and on 5-HT(1A) and 5-HT(1B) autoreceptor sensitivity, using in vivo microdialysis in the rat. The effects of T3 on postsynaptic 5-HT(1A) receptor activity in the hypothalamus were also determined using a neuroendocrine challenge procedure. T3 administered daily at 20 microg/kg s.c. for 2 weeks reduced the sensitivity of 5-HT(1A) autoreceptors which control 5-HT release, as measured by the effect of 8-OH-DPAT to decrease 5-HT in the hypothalamus, and also the sensitivity of hypothalamic 5-HT(1B) receptors as measured by the effect of the 5-HT(1B) receptor agonist CP 93129 to decrease 5-HT release. Imipramine at 10 mg/kg daily for 4 weeks by osmotic minipump reduced 5-HT(1A) autoreceptor activity, as measured by the effect of 8-OH-DPAT in the hypothalamus, but the combination of T3 and imipramine given for 2 weeks did not affect either 5-HT(1A) or 5-HT(1B) autoreceptor activity. T3 at 20 microg/kg s.c. given daily for 1 week also reduced the sensitivity of postsynaptic 5-HT(1A) receptors in the hypothalamus, as measured by injection of 8-OH-DPAT and determination of the plasma ACTH and corticosterone responses. Animals which received T3 for 7 days showed a dose-dependent reduction in plasma free T4 levels but no change in total T3 levels. We conclude that while T3 alone affects both presynaptic and postsynaptic components of the serotonergic system, these effects may not be responsible for the therapeutic acceleration action seen with a combination of a tricyclic drug and T3.
Gur
Eitan
E
Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah-Hebrew University Medical Center, P.O. Box 12000, 91120 Jerusalem, Israel.
Lifschytz
Tsuri
T
Van De Kar
Louis D
LD
Lerer
Bernard
B
Newman
Michael E
ME
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D017660:Autoreceptors / Q000187:drug effects* / Q000378:metabolism; D003345:Corticosterone / Q000378:metabolism; D004347:Drug Interactions; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D007099:Imipramine / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D008845:Microinjections; D051381:Rats; D011919:Rats, Inbred Strains; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects* / Q000378:metabolism; D044302:Receptor, Serotonin, 5-HT1B / Q000187:drug effects* / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects; D014284:Triiodothyronine / Q000008:administration & dosage / Q000502:physiology*
D000929:Antidepressive Agents, Tricyclic; D017660:Autoreceptors; D044302:Receptor, Serotonin, 5-HT1B; D017366:Serotonin Receptor Agonists; D014284:Triiodothyronine; D044282:Receptor, Serotonin, 5-HT1A; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000324:Adrenocorticotropic Hormone; D007099:Imipramine; D003345:Corticosterone