The impact of scopolamine pretreatment on 3-iodothyronamine (T1AM) effects on memory and pain in mice

We previously demonstrated that 3-iodothyronamine (T1AM), a by-product of thyroid hormone metabolism, pharmacologically administered to mice acutely stimulated learning and memory acquisition and provided hyperalgesia with a mechanism which remains to be defined. We now aimed to investigate whether the T1AM effect on memory and pain was maintained in mice pre-treated with scopolamine, a non-selective muscarinic antagonist expected to induce amnesia and, possibly, hyperalgesia. Mice were pre-treated with scopolamine and, after 20 min, injected intracerebroventricularly (i.c.v.) with T1AM (0.13, 0.4,1.32 gg/kg). 15 min after TIAM injection, the mice learning capacity or their pain threshold were evaluated by the light/dark box and by the hot plate test (51.5 C) respectively. Experiments in the light/dark box were repeated in mice receiving clorgyline (2.5 mg/kg, i.p.), a monoamine oxidase (MAO) inhibitor administered 10 min before scopolamine (0.3 mg/kg). Our results demonstrated that 0.3 mg/kg scopolamine induced amnesia without modifying the murine pain threshold. T1AM fully reversed scopolamine-induced amnesia and produced hyperalgesia at a dose as low as 0.13 pg/kg. The TIAM anti-amnestic effect was lost in mice pre-treated with clorgyline. We report that the removal of muscarinic signalling increases T1AM pro learning and hyperalgesic effectiveness suggesting TIAM as a potential treatment as a pro-drug for memory dysfunction in neurodegenerative diseases. (C) 2017 Elsevier Inc. All rights reserved.