Differently Directed Influences of Semax on the Formation and Functional Impairments of an Active Avoidance Reaction in Rats
Short-term effects of the synthetic nootropic peptide Semax on the content and metabolism of monoamines in the brain of C57/Bl 6 mice and Sprague–Dawley rats were studied. Intraperitoneal injection of Semax at a dose of 0.15 mg/kg caused an increase in the tissue concentrations of 5-hydroxyindoleacetic acid (5-HIAA) in the hypothalamus and striatum of mice 0.5 and 2 h after the injection. Using brain microdialysis, we detected increased levels of extracellular 5-HIAA in the striatum of freely moving rats 1 h after administration of 0.15 or 0.6 mg/kg Semax. The effect lasted for an additional 3 h. These data suggest that Semax produces a modulatory effect on the serotoninergic systems of the animal brain, increasing the turnover rate of serotonin. The search for drugs improving memory and enhancing cognitive functions in humans, and the study of the mechanisms of their effects are an important scientific problem. Semax, a recently developed nootropic drug, is a synthetic peptide Met–Glu–His–Phe–Pro– Gly–Pro, structurally analogous to region 4–10 of adrenocorticotropic hormone (ACTH) but devoid of its hormonal activity . The Pro–Gly–Pro segment of Semax is responsible for its metabolic stability and the relatively long duration of its nootropic effect. As shown in a number of studies, Semax improves learning and memory in animals, increases the concentration and attention during information processing, and relieves mental fatigue in humans [1, 2]. However, the neurochemical mechanisms of Semax effects are still far from clear. Recent studies demonstrated that various ACTH analogues, including Semax, possess the properties of antagonists of melanocortin (MC) receptors . Convincing evidence has been provided for the existence of close functional and anatomical links between the melanocortin and monoaminergic systems of the brain [4, 5]. Intracerebroventricular administration of α -melanocyte-stimulating hormone induces grooming behavior in rats and simultaneously raises the intracellular level of dopamine in the striatum .