BACKGROUND AND PURPOSE3-Iodothyronamine (T1AM), an endogenous derivative of thyroid hormones, is regarded as a rapid modulator of behaviour and metabolism. To determine whether brain thyroid hormone levels contribute to these effects, we investigated the effect of central administration of T1AM on learning and pain threshold of mice either untreated or pretreated with clorgyline (2.5 mg·kg -1 , i.p.), an inhibitor of amine oxidative metabolism. EXPERIMENTAL APPROACHT1AM (0.13, 0.4, 1.32 and 4 mg·kg -1 ) or vehicle was injected i.c.v. into male mice, and after 30 min their effects on memory acquisition capacity, pain threshold and curiosity were evaluated by the following tests: passive avoidance, licking latency on the hot plate and movements on the hole-board platform. Plasma glycaemia was measured using a glucorefractometer. Brain levels of triiodothyroxine (T3), thyroxine (T4) and T1AM were measured by HPLC coupled to tandem MS. ERK1/2 activation and c-fos expression in different brain regions were evaluated by Western blot analysis. RESULTST1AM improved learning capacity, decreased pain threshold to hot stimuli, enhanced curiosity and raised plasma glycaemia in a dose-dependent way, without modifying T3 and T4 brain concentrations. T1AM effects on learning and pain were abolished or significantly affected by clorgyline, suggesting a role for some metabolite(s), or that T1AM interacts at the rapid desensitizing target(s). T1AM activated ERK in different brain areas at lower doses than those effective on behaviour. CONCLUSIONS AND IMPLICATIONST1AM is a novel memory enhancer. This feature might have important implications for the treatment of endocrine and neurodegenerative-induced memory disorders. AbbreviationsCREB, cyclic AMP-responsive element binding; PBST, PBS plus Tween; T1AM, 3-iodothyronamine; T3, triiodothyroxine; T4, thyroxine; TA1 receptor, trace amine-associated receptor 1

BACKGROUND AND PURPOSE3-Iodothyroacetic acid (TA1) is an end product of thyroid hormone metabolism. So far, it is not known if TA1 is present in mouse brain and if it has any pharmacological effects. EXPERIMENTAL APPROACHTA1 levels in mouse brain were measured by HPLC coupled to mass spectrometry. After i.c.v. administration of exogenous TA1 (0.4, 1.32 and 4 μg·kg −1 ) to mice, memory acquisition-retention (passive avoidance paradigm with a light-dark box), pain threshold to thermal stimulus (51.5°C; hot plate test) and plasma glucose (glucorefractometer) were evaluated. Similar assays were performed in mice pretreated with s.c. injections of the histamine H1 receptor antagonist pyrilamine (10 mg·kg ) and the corresponding WT strain. KEY RESULTSTA1 was found in the brain of CD1 but not of HDC mice. Exogenous TA1 induced amnesia (at 0.4 μg·kg ). All these effects were modulated by pyrilamine and zolantidine. In HDC −/− mice, TA1 (1.32 and 4 μg·kg −1) did not increase plasma glucose or induce hyperalgesia. CONCLUSIONS AND IMPLICATIONSBehavioural and metabolic effects of TA1 disclosed interactions between the thyroid and histaminergic systems. AbbreviationsT3, tri-iodothyronine; TA1, 3-iodothyroacetic acid; TA1M, 3-iodothyronamine; TRIAC, tri-iodothyroacetic acid

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Objective-The activation of nuclear factor-B (NF-B) is a crucial step in the arterial wall's response to injury. The identification and characterization of the NF-B essential modulator-binding domain (NBD) peptide, which can block the activation of the IB kinase complex, have provided an opportunity to selectively abrogate the inflammation-induced activation of NF-B. The aim of the present study was to evaluate the effect of the NBD peptide on neointimal formation. Methods and Results-In the rat carotid artery balloon angioplasty model, local treatment with the NBD peptide (300 g/site) significantly reduced the number of proliferating cells at day 7 (by 40%; PϽ0.01) and reduced injury-induced neointimal formation (by 50%; PϽ0.01) at day 14. These effects were associated with a significant reduction of NF-B activation and monocyte chemotactic protein-1 expression in the carotid arteries of rats treated with the peptide. In addition, the NBD peptide (0.01 to 1 mol/L) reduced rat smooth muscle cell proliferation, migration, and invasion in vitro. Similar results were observed in apolipoprotein E Ϫ/Ϫ mice in which the NBD peptide (150 g/site) reduced wire-induced neointimal formation at day 28 (by 47%; PϽ0.01). Conclusion-The