Brain monoamine synthesis and receptor sensitivity after single or repeated administration of thyroxine

Summary

The effects of various pretreatment schedules with L-thyroxine (T₄) on endogenous brain concentrations of catecholamines (CA) and 5-hydroxy-tryptamine (5-HT) as well as their respective synthesis ratesin vivo and the sensitivity of CA-and 5-HT receptors, respectively, were investigated. None of the T₄ pretreatments had any significant effect on the brain concentrations of noradrenaline, dopamine or 5-HT. The CA-and 5-HT synthesis rates were significantly increased by 2, 3, or 4 s.c. injections but not by 1 injection of T₄ (1 mg/kg, 12 hours intervals, 6 hours after the last T₄ injection), as indicated by increased accumulations of DOPA and 5-hydroxytryptophan (5-HTP), respectively, during 30 min following complete inhibition of their decarboxylation. The CA receptor sensitivity seemed to be increased following 3 or 4 injections of T₄, but not after 1 or 2 injections, as indicated by a significantly increased response (i.e. locomotor stimulation) to a dopamine receptor agonist (ET 495, 20 mg/kg i.p.)plus a NA receptor agonist (clonidine, 2 mg/kg i.p.) in mice made deficient in CA by pretreatment with reserpine (10 mg/kg i.p. 6 hours) and a tyrosine hydroxylase inhibitor (DL-α-methyl-p-tyrosine methylester, 250 mg/ kg i.p., 1 hour). In contrast, the sensitivity of central 5-HT receptors seemed not to be altered by 4 injections of T₄, as indicated by an unchanged response (i.e. locomotor stimulation) to DL-5-HTP (75 mg/kg i.p.) following inhibition of peripheral but not central decarboxylase. Thus, the presynaptic event, the increased CA synthesis rate, preceded in onset the probably postsynaptic event, the increased CA receptor sensitivity, suggesting different mechanisms to be involved in the two phenomena. The increased synthesis rate of both CA and 5-HT may reflect a generally increased metabolism in the hyperthyroid state. Since the CA-but not the 5-HT receptors in our tests showed increased sensitivity, the former effect may be a specific effect of T₄,i.e., not reflecting a generally increased receptor sensitivity.