The influence of L-triiodothyronine (T3) on the effects of repeated administration of desipramine or electroconvulsive shock on alpha 2- and beta-adrenoceptor function in the brain of the rat: implications for the potentiation of antidepressant therapy by T3.
Repeated, daily administration of either an electroconvulsive shock (ECS; 110 V, 1 sec) or desipramine (DMI; 5 mg/kg X 2) to rats caused a progressive decrease in the function of presynaptic alpha 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 (T3; 100 micrograms/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 T3 did not affect the hypoactivity responses. alpha 2-Adrenoceptors, measured by the binding of [3H]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 alpha 2-adrenoceptors induced by DMI or electroconvulsive shock but may have delayed the onset produced by DMI. Binding to beta-adrenoceptors in the cortex was measured using [3H]dihydroalprenolol. This was significantly decreased by 14 days administration of DMI, but not significantly by electroconvulsive shock for 10. Down-regulation of beta-adrenoceptors, induced by DMI was rapid, being observed after 1 day of treatment. Injection of T3 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 beta-adrenoceptors 24 hr after injection.(ABSTRACT TRUNCATED AT 250 WORDS)
Heal
D J
DJ
MRC Unit, Radcliffe Infirmary, Oxford, U.K.
Bristow
L J
LJ
Elliott
J M
JM
Bloomfield
J G
JG
Catto
L C
LC
Atterwill
C K
CK
D000818:Animals; D001921:Brain / Q000187:drug effects*; D003000:Clonidine / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology*; D004082:Dihydroalprenolol / Q000378:metabolism; D004146:Dioxanes / Q000378:metabolism; D004597:Electroshock; D019329:Idazoxan; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D014284:Triiodothyronine / Q000494:pharmacology*
D004146:Dioxanes; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D014284:Triiodothyronine; D004082:Dihydroalprenolol; D003000:Clonidine; D003891:Desipramine; D019329:Idazoxan