3-Iodothyroacetic acid (TA1), a by-product of thyroid hormone metabolism, reduces the hypnotic effect of ethanol without interacting at GABA-A receptors

3-iodothyroacetic acid (TA1) is among the by-products of thyroid hormone metabolism suspected to mediate the non-genomic effects of the hormone (T3). We aim to investigate whether TA1 systemically administered to mice stimulated mice wakefulness, an effect already described for T3 and for another T3 metabolite (i.e. 3-iodothryonamine; T1AM), and whether TA1 interacted at GABA-A receptors (GABA-AR). Mice were pre-treated with either saline (vehicle) or TA1 (1.32, 4 and 11 μg/kg) and, after 10 min, they received ethanol (3.5 g/kg, i.p.). In another set of experiments, TA1 was administered 5 min after ethanol. The latency of sleep onset and the time of sleep duration were recorded. Voltage-clamp experiments to evaluate the effect of 1 μM TA1 on bicuculline-sensitive currents in acute rat hippocampal slice neurons and binding experiments evaluating the capacity of 1, 10, 100 μM TA1 to displace [3H]flumazenil from mice brain membranes were also performed. 4 μg/kg TA1 increases the latency of onset and at 1.32 and 4 μg/kg it reduces the duration of ethanol-induced sleep only if administered before ethanol. TA1 does not functionally interact at GABA-AR. Overall these results indicate a further similarity between the pharmacological profile of TA1 and that of T1AM.