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Thyroxine and brain catecholamines: Increased transmitter synthesis and increased receptor sensitivity

1974; Elsevier BV; Volume: 77; Issue: 3 Linguagem: Inglês

10.1016/0006-8993(74)90635-0

1872-6240

Gunnar Engstro ̈m, Torgny H. Svensson, Bertil Waldeck,

Memory and Neural Mechanisms

Mice were given 8 subcutaneous injections of 20 μg ofl-thyroxine sodium (T4) at 12 h intervals. One hour after the last injection the brain concentration of noradrenaline (NA), but not of dopamine (DA), was significantly reduced. The accumulation of DOPA in the brain during 30 min after treatment with the aromatic amino acid decar☐ylase inhibitor NSD 1015 (150 mg/kg) was significantly enhanced 5 and 15 h after the last T4 injection, indicating increased synthesis of brain catecholamines (CA). Twelve hours after the last T4 administration, the brain accumulation of homovanillic acid following treatment with probenecid (200 mg/kg, 2 h) was twice the control value. At the same time interval the net accumulation of [3H]DA and [3H]NA formed in the brain from [3H]tyrosine (10 μg/kg i.v., 10 min) was significantly increased by T4. The specific activity of [3H]tyrosine in plasma was, in these experiments, slightly reduced. The plasma level of thyroxine was increased, when measured 2–12 h after the last thyroxine injection, but no correlation was found between the plasma level and the rate of CA synthesis in the brain. The T4 regimen caused significant cardiomegaly. Six hours after the last T4 injection, the exploratory or the spontaneous locomotor activity of mice was not affected. However, in mice pretreated with reserpine (10 mg/kg, 6 h) or reserpineplusd, l-α-methyl-p-tyrosinemethylester (250 mg/kg, 1 h), the locomotor stimulant action of the DA-receptor activating drug, ET 495 (20 mg/kg), plus the NA-receptor stimulant drug, clonidine (2 mg/kg), was significantly enhanced by the T4 regimen. The data imply increased turnover of brain CA following pretreatment with thyroxine, as well as increased sensitivity of brain CA receptors.