The influence of l-triiodothyronine (T3) on the effects of repeated administration of desipramine or electroconvulsive shock on α2- and β-adrenoceptor function in the brain of the rat: Implications for the potentiation of antidepressant therapy by T3

Abstract Repeated, daily administration of either an electroconvulsive shock (ECS; 110 V, 1 sec) or desipramine (DMI; 5 mg kg × 2) to rats caused a progressive decrease in the function of presynaptic α 2 -adrenoceptors, assessed by the hypoactivity (sedation) response to clonidine (0.2 mg kg ). This attenuation required approximately 7 days' administration of either treatment for maximum effect. A single injection of triiodothyronine (T 3 ; 100 μg kg ) on day 1 of the treatment markedly accelerated the decreased responses to clonidine induced by DMI or electroconvulsive shock, but did not alter the maximum attenuation. By itself T 3 did not affect the hypoactivity responses. α 2 -Adrenoceptors, measured by the binding of [ 3 H]idazoxan in the cortex, which are believed to be predominantly postsynaptic, were decreased by 14 days of DMI or electroconvulsive shock for 10 days, but not 2 days of either treatment. Triiodothyronine did not influence the decreased number of α 2 ,-adrenoceptors induced by DMI or electroconvulsive shock but may have delayed the onset produced by DMI. Binding to β-adrenoceptors in the cortex was measured using [ 3 H]dihydroalprenolol. This was significantly decreased by 14 days administration of DMI, but not significantly by electroconvulsive shock for 10. Down-regulation of β-adrenoceptors, induced by DMI was rapid, being observed after 1 day of treatment. Injection of T 3 did not influence the final decreases produced by DMI or electroconvulsive shocks but moderately delayed their onset. Triiodothyronine alone caused a 25% reduction in cortical β-adrenoceptors 24 hr after injection. The results demonstrate, therefore, that T 3 does influence some of the pharmacological actions of antidepressant treatments and these are discussed with reference to the reported potentiation by T 3 of the clinical efficacy of tricyclic antidepressants.