Decreased in vivo conversion ratios (T 3/T 4 ratios) suggest that acute DMI treatment causes a significant decrease in 5′-deiodinase activity in balance of brain (but not cerebellum) in all DMI treated rats as compared to their saline treated controls (ANOVA, P < 0.0001). To investigate further the effects of DMI on brain processing of TH, we have measured effects of the drug on vivo rates of T 4 to T 3 conversion in a series of experiments in which DMI (25 mg/kg) was given to HYPO, EU and HYPER male rats in conjunction with i.v. Recently we have reported that a single dose of DMI significantly decreases brain uptake of both thyroxine (T 4) and 3,3′,5-triiodothyronine (T 3) across the spectrum of thyroid states from hypothyroid (HYPO) to euthyroid (EU) to T 4-induced hyperthyroid (HYPER). An acute dose of DMI has been used in order to determine the primary effects of the drug in brain without perturbations from secondary effects. We have studied the effects of desmethylimipramine (DMI), a tricyclic antidepressant, on thyroid hormone (TH) handling in rat brain in an effort to discover a pharmacological basis for reported interactions between TH, affective disorders and psychotropic drugs.
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