3-iodothyroacetic acid (TA1), an end metabolite of thyroid hormone, stimulates mice attention and vigilance: new evidence for the involvement of the histamine-thyroid axes

Background and Purpose: We recently reported 3-iodothyroacetic acid (TA1), a metabolite of thyroid hormone, stimulated learning and gave hyperal-gesia activating the histaminergic system. We now aim to investigate whether TA1 could induce other typical histamine-dependent effects including increase of attention of vigilance and of wakefulness. Experimental Approach: CD1 male mice received i.p. TA1 (1.32, 4 and 11 μgkg-1) or saline and, after 15 min, spontaneous locomotor activity, motor coordination, and the immobility time were evaluated on the hole board, the rota road and the forced swim test respectively. The effect of TA1 (1.32, 4 and 11 μgkg-1 i.p.) on the sleeping time of mice receiving an acute dose of ethanol (3.5 mgkg-1; i.p.) was evaluated. The experiments were repeated in mice pre-treated with pyrilamine (10 mgkg-1) or zolantidine (5 mgkg-1).Hypothalamic levels of p-mTOR and p-GSK-3 beta in mice receiving 4 μgkg-1 TA1 or saline in the absence or presence of immepip (5 mgkg-1) (a type 3 histamine receptor agonist) were measured by Western blot.Key Results: TA1 (4 and 11 μgkg-1; i.p.) increased mice spontaneous locomotor activity, reduced the immobility time in the forced swim test with-out giving motor incoordination, effects reverted by zolantidine and pyrilamine respectively. TA1 (4 μgkg-1) significantly delayed the onset and shortened the duration of ethanol-induced sleep. At the same dose TA1 increased hypo-thalamic p-mTOR and p-GSK-3 beta levels, an effect prevented by immepip pre-treatment.Downloaded from Bioscientifica.com at 03/07/2022 10:23:22AMvia free access