Effect of amitriptyline on the messenger RNA of thyroid hormone-responsivegenes in rat cerebral tissue

To determine the molecular mechanisms of the potentiating effect of thyroid hormones (TH) on the therapeutic efficacy of tricyclic antidepressants (TC A), the expression of two known TH-responsive mRNAs was measured in control rats and rats treated with triiodothyronine (T-3, 10 mu g/100 g for 10 day s), amitriptyline (10 mg/kg for 10 days), or combined T-3 and amitriptyline . Northern blot analysis was carried out to measure the cerebral tissue con tent of a novel translational repressor (NAT-1) and another thyroid hormone -responsive (THR) mRNA. Rats treated with the combination of T-3 and amitri ptyline had significantly higher NAT-I expression (2691.1+/-134.1 arbitrary units) than rats treated with T-3 only (1688.5+/-77.8) or with amitriptyli ne only (1452.5+/-87.5) or the untreated control rats (731.3+/-23.0), P<0.0 1. Amitriptyline treatment did not alter the expression of THR mRNA or THR protein in either control or T-3-treated rats. It is concluded that alterat ions in the expression of selective T-3 responsive genes in cerebral tissue could be a mechanism of the known T-3 potentiation of the therapeutic effi cacy of TCA.