Pharmacological effects of 3-iodothyronamine (T1AM) in mice include facilitation of memory acquisition and retention and reduction of pain threshold.
OBJECTIVE
3-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.


METHODS
T1AM (0.13, 0.4, 1.32 and 4 μg·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.


RESULTS
T1AM 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
T1AM is a novel memory enhancer. This feature might have important implications for the treatment of endocrine and neurodegenerative-induced memory disorders.
Department of Pharmacology, University of Florence, Florence, Italy.
Maria Elena
ME
Manni
Gaetano
G
De Siena
Alessandro
A
Saba
Maja
M
Marchini
Elisa
E
Landucci
Elisabetta
E
Gerace
Marina
M
Zazzeri
Claudia
C
Musilli
Domenico
D
Pellegrini-Giampietro
Rosanna
R
Matucci
Riccardo
R
Zucchi
Laura
L
Raimondi
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D006358:Hot Temperature; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects*; D051379:Mice; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology; D017288:Pain Threshold / Q000187:drug effects*; D013963:Thyroid Hormones / Q000378:metabolism; D013970:Thyronines / Q000494:pharmacology*
C487948:3-iodothyronamine; D013963:Thyroid Hormones; D013970:Thyronines