Effect of amitriptyline on the messenger RNA of thyroid hormone-responsive genes in rat cerebral tissue.
To determine the molecular mechanisms of the potentiating effect of thyroid hormones (TH) on the therapeutic efficacy of tricyclic antidepressants (TCA), the expression of two known TH-responsive mRNAs was measured in control rats and rats treated with triiodothyronine (T3, 10 microg/100 g for 10 days), amitriptyline (10 mg/kg for 10 days), or combined T3 and amitriptyline. Northern blot analysis was carried out to measure the cerebral tissue content of a novel translational repressor (NAT-1) and another thyroid hormone-responsive (THR) mRNA. Rats treated with the combination of T3 and amitriptyline had significantly higher NAT-1 expression (2691.1+/-134.1 arbitrary units) than rats treated with T3 only (1688.5+/-77.8) or with amitriptyline only (1452.5+/-87.5) or the untreated control rats (731.3+/-23.0), P<0.01. Amitriptyline treatment did not alter the expression of THR mRNA or THR protein in either control or T3-treated rats. It is concluded that alterations in the expression of selective T3 responsive genes in cerebral tissue could be a mechanism of the known T3 potentiation of the therapeutic efficacy of TCA.
Mooradian
A D
AD
Department of Internal Medicine, St Louis University Medical School, MO 63104, USA.
Li
J P
JP
D048868:Adaptor Proteins, Signal Transducing; D000639:Amitriptyline / Q000494:pharmacology*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001835:Body Weight; D001923:Brain Chemistry / Q000187:drug effects* / Q000235:genetics; D018076:DNA, Complementary; D004435:Eating; D015870:Gene Expression / Q000187:drug effects; D018398:Homeodomain Proteins / Q000235:genetics*; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D012097:Repressor Proteins / Q000235:genetics*; D014284:Triiodothyronine / Q000235:genetics / Q000494:pharmacology*
C109099:Abi2 protein, rat; D048868:Adaptor Proteins, Signal Transducing; D000929:Antidepressive Agents, Tricyclic; D018076:DNA, Complementary; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D014284:Triiodothyronine; D000639:Amitriptyline