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Neurochemical Research, Vol. 30, No. 12, December 2005 ( 2005), pp. 14931500
DOI: 10.1007/s11064-005-8826-8Semax, An ACTH(4-10) Analogue with Nootropic Properties,
Activates Dopaminergic and Serotoninergic Brain Systemsin Rodents*Kirill O. Eremin,1,2,5 Vladimir S. Kudrin,1 Pirjo Saransaari,2 Simo S. Oja,2,3
Igor A. Grivennikov,4 Nikolay F. Myasoedov,4 and Kirill S. Rayevsky1(Accepted June 22, 2005)Corticotrophin (ACTH) and its analogues, particularly Semax (Met-Glu-His-Phe-Pro-Gly-
Pro), demonstrate nootropic activity. Close functional and anatomical links have been
established between melanocortinergic and monoaminergic brain systems. The aim of present
work was to investigate the eects of Semax on neurochemical parameters of dopaminergicand serotonergic systems in rodents. The tissue content of 5-hydroxyindoleacetic acid
(5-HIAA) in the striatum was signicantly increased (+25%) 2 h after Semax administration.
The extracellular striatal level of 5-HIAA gradually increased up to 180% within 14 h after
Semax (0.15 mg/kg, ip) administration. This peptide alone failed to alter the tissue and
extracellular concentrations of dopamine and its metabolites. Semax injected 20 min priorD-amphetamine dramatically enhanced the effects of the latter on the extracellular level of
dopamine and on the locomotor activity of animals. Our results reveal the positive modulatory
effect of Semax on the striatal serotonergic system and the ability of Semax to enhance both
the striatal release of dopamine and locomotor behavior elicited by D-amphetamine.KEY WORDS: 3,4-Dihydroxyphenylacetic acid; 5-hydroxyindoleacetic acid; ACTH analogues; cognitive
enhancers; D-amphetamine; dopamine; dopamine receptors; locomotor activity; melanocortin receptors;
neurotrophic factors; Semax; serotonin.challenging scientic problem. The investigations of
de Wied initiated studies that demonstrated the role of
corticotropin (ACTH) and its fragments in conditioned behavior (1). Further, it was shown that ACTH
and its analogues display noortopic properties,
improve memory and learning processes (24). The
ACTH(47) fragment appeared to be the shortest
sequence required to inuence mammalian behavior,
exhibiting the same potency as ACTH(410) (3). A
number of ACTH analogues have been synthesized.
Some of them are more stable and more potent than
the natural N-terminal ACTH fragments (3,5).
Among these analogues, ORG 2766 [H-Met(O2)-Glu-
His-Phe-D-Lys-Phe-OH] has been investigated most
intensively and became the prototype in studies on theINTRODUCTIONThe search for drugs improving memory and
enhancing cognitive functions in humans and the
study of mechanisms of their action seem to be a* Special issue dedicated to Dr. Simo S. Oja.1 V.V. Zakusovs Research Institute of Pharmacology RAMS,Moscow, Russia.2...