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 μg/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.