Differently Directed Influences of Semax on the Formation and Functional Impairments of an Active Avoidance Reaction in Rats

Abstract

ACTH/MSH-like peptides (melanocortins) play an important role in regulating many body functions, including CNS functions. The current literature includes extensive data on the influences of melanocortins on the acquisition of conditioned reflexes. Studies of the actions of melanocortins on the acquisition of reflexes with positive reinforcement have unambiguously demonstrated enhancing effects [24]. Experiments using a model with negative (pain) reinforcement did not yield unambiguous results. Various authors have shown that melanocortins have both positive [25] and negative influences on learning [20].The nootropic effects of natural ACTH fragments are transient and are only seen with the most active of these compounds -that of ACTH(4-10) lasts some 30-60 min [1]. Many investigators have attempted to increase the efficacy of natural melanocortins by introducing structural modifications. These experiments produced analogs of natural peptides lacking hormonal effects had having marked activity [18]. However, none of these analogs has found use in clinical practice.Semax -an analog of the ACTH(4-10) fragment whose structure includes the ACTH(4-7) fragment and the tripeptide Pro-Gly-Pro occupies an important position among the synthetic melanocortins. Animal experiments have shown that this peptide, like natural melanocortins, has a wide spectrum of neurotropic activities [12]. Semax improves learning in animals and the duration of its effect is at least 20 h [1]. This peptide is currently used as a nootropic and neuroprotective agent. Despite the fact that medicines developed on the basis of Semax have been used in clinical practice for more than 15 years, studies of the physiological effects of the peptide continue. The relevance of these studies comes from the need to explain the mechanisms of action of Semax and the potential for widening the spectrum of its clinical application.Animal experiments have repeatedly shown that Semax has positive effects on learning with positive reinforcement [16].The effects of Semax on the formation of a conditioned active avoidance reaction were studied in rats using different experimental models. I.p. administration of Semax at a dose of 0.05 mg/kg was found to accelerate the acquisition of a one-way conditioned avoidance reaction in a model of an active pain stimulus avoidance reflex in which the animals had to jump onto a shelf. In animals trained in a shuttle box, the peptide increased the threshold current required to provoked movement of the rats across the chamber and slowed acquisition of a two-way active avoidance reaction. Semax stimulated reproduction of the avoidance reaction in the shuttle box in rats after functional impairment induced by acute changes in cause-effect and spatial relationships in the experimental environment. These data support the view that this peptide has nootropic properties.

Microbiological Production of Isocitric Acid from Biodiesel Waste and Its Effect on Spatial Memory

“…The spatial transformation of the CAAR used in this study is a more difficult task for animals than the development of avoidance responses. The drug Semax having antioxidant activity enhances the reproduction of avoidance responses after spatial transformation [58]. Taking into account the above information, the results of this study suggest that the spatial transformation of the CAAR causes oxidative stress in the tested animals and that the observed beneficial effect of ICA is explained by its antioxidant activity.…”