Desmethylimipramine, a potent inhibitor of synaptosomal norepinephrine uptake, has diverse effects on thyroid hormone processing in rat brain. I. Effects on in vivo uptake of 125I-labeled thyroid hormones in rat brain

Abstract

Several lines of evidence point to an interaction between amine uptake inhibitors (tricyclic antidepressants) and thyroid hormones. To examine this issue under conditions which would minimize secondary effects of drug treatment, desmethylimipramine (DMI), a highly specific norepinephrine uptake inhibitor, was given acutely as a single i.p. dose one hour before i.v. [ 125I]triidothyronine (T 3 *) or [ 125I]thyroxine (T 4 *). Tissues were analysed after rat decapitation at 3, 5, 10, and 20 min intervals thereafter. DMI had a small but significant inhibitory effect on the brain uptake of both T 3 * (7.4%) and T 4 * (19%) over their respective 20-min time courses as indicated by two-way ANOVA. To examine the drug response further and to determine the effect of thyroid status on the response, hypothyroid (HYPO) and T 4-induced hyperthyroid (HYPER) rats, were given i.v. T 3 * and, 5 min later, i.p. DMI or saline. They were killed 3 h later and tissues analysed. Because DMI effects on T 4 * uptake could not be evaluated over a 3 h period without blocking T 4 * to T 3 * conversion, sodium ipodate (60 mg/kg) was given in 2 doses before i.v. T 4 *. Under these conditions, DMI significantly reduced brain concentrations of the administered T 3 * and T 4 * in HYPO (15% and 19%) and HYPER rats (13% and 25%). These results suggest that, as it does in the case of norepinephrine, DMI blocks the uptake site for T 3 and T 4 in rat brain. No information is available regarding the relationship, if any, between the thyroid hormone and norepinephrine uptake sites.