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

Abstract 3-iodothyroacetic acid (TA 1 ) 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 TA 1 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 TA 1 interacted at GABA-A receptors (GABA-AR). Mice were pre-treated with either saline (vehicle) or TA 1 (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, TA 1 was administered 5 min after ethanol. The latency of sleep onsetand the time of sleep duration were recorded. Voltage-clamp experiments to evaluate the effect of 1 μM TA 1 on bicuculline-sensitive currents in acute rat hippocampal slice neurons and binding experiments evaluating the capacity of 1, 10, 100 μM TA 1 to displace [ 3 H] flumazenilfrom mice brain membranes were also performed. 4 μg/kg TA 1 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. TA 1 does not functionally interact at GABA-AR. Overall these results indicate a further similarity between the pharmacological profile of TA 1 and that of T 1 AM.