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Effects of Semax on Dopaminergic and Serotoninergic Systems of the Brain
... Acquisition of the reaction in this case required more presentations of the conditioned and unconditioned stimuli than in one-way avoidance, such that the rat received a larger number of painful stimuli, including unavoidable stimuli. Previous studies have shown that unavoidable painful electrical stimulation, like administration of ACTH and ACTH (4)(5)(6)(7)(8)(9)(10), improves the reproduction of a previously acquired reflex with negative reinforcement [21]. The authors suggested that these effects were linked with the ability of melanocortins to facilitate extraction of memory traces related to negative stimuli. ...
... The possible mechanisms of the differently directed effects of Semax on formation of the two-way avoidance reaction and the recovery of this reaction after functional impairment suggest the following. It has now been shown that Semax increases the activity of the brain serotoninergic system [5]. The involvement of the serotoninergic system in mediating the effects of Semax is also evidenced by the decrease in the analgesic effect of the peptide by the nonselective serotonin receptor blocker cyproheptadine [12]. ...
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.
... Кроме того, BDNF участвует в регуляции тревожных и стрессорных расстройств, и за счет изменения его экспрессии может реализовываться анксиолитический эффект пептида [21]. Его участие в модуляции реакции тревоги и депрессии у экспериментальных животных также возможно вследствие влияния пептида на системы биогенных аминов головного мозга [22]. ...
ACTH4–7-PGP peptide has a wide range of neurotropic effects, including anxiolytic and antidepressant effects in stress conditions. At the same time, one of the important issues is to clarify the role of corticosterone in behavioral reactions against the background of repeated administration of ACTH4–7-PGP in chronic stress. The aim of the study was to study the effect of ACTH4–7-PGP on behavior and corticosterone level in rats and their relationship under chronic stress. ACTH4–7-PGP was administered to male Wistar rats at doses of 5, 50, 150, 450 μg/kg for 14 days 12–15 minutes before stress exposure. The behavior of animals was studied in open field test and elevated plusmaze test, the concentration of corticosterone was determined with ELISA. It was found that the peptide under conditions of chronic stress had an anxiolytic effect and reduced anxiety levels at doses of 50 and 150 μg/kg (p < 0.05–0.01). In all doses used, ACTH4–7-PGP reduced the concentration of corticosterone in the blood serum of
stressed rats by 28.6–34.2% (p < 0.05). Correlation analysis showed that after administration of ACTH4–7-PGP at a dose of 50 μg/kg, a decrease in anxiety had a direct strong association with a decrease in corticosterone levels.
... Also, this group showed a significant decrease in DA turnover (DOPAC/DA) compared to the group receiving MPTP alone (data not shown). Given that SEMAX does not affect the striatal DA level [12], the obtained data indicate a neuroprotective effect of SEMAX on DA-ergic neurons; however, to enhance this effect, the experiment design should be altered; e.g., through use of multiple injections of the agent. ...
Degeneration of nigrostriatal dopaminergic neurons in Parkinson's disease begins from the axonal terminals in the striatum and, then, in retrograde fashion, progresses to the cell bodies in the substantia nigra. Investigation of the dynamics of axonal terminal degeneration may help in the identification of new targets for neuroprotective treatment and be used as a tool for testing potential drugs. We have shown that the degeneration rate of dopaminergic axonal terminals changes over time, and that the striatal dopamine concentration is the most sensitive parameter to the action of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). This model was validated using neuroprotectors with well-known mechanisms of action: the dopamine transporter inhibitor nomifensine and SEMAX peptide that stimulates the secretion of endogenous neurotrophic factors or acts as an antioxidant. Nomifensine was shown to almost completely protect dopaminergic fibers from the toxic effect of MPTP and maintain the striatal dopamine concentration at the control level. However, SEMAX, slightly but reliably, increased striatal dopamine when administered before MPTP treatment, which indicates that it is more effective as an inductor of endogenous neurotrophic factor secretion rather than as an antioxidant.
... It benefits in protecting brain cells, so that it can optimize the metabolic processes of the brain cells and improve cognitive function. It is an antioxidant and can synthesize some proteins in brain [8][9][10]. Due to these reasons, in this research semax peptide was used as an alternative therapy, in order to study the potency of it in reducing MDA levels and improvement of proteins profiles on brain of epilepsy rats. ...
... Chronic daily administration of Semax (600 μg/kg per day) for 7 days tended to reduce the levels of dopamine and serotonin significantly in the hypothalamus. These findings suggest the accelerated turnover of serotonin, reflecting an increase in the functional activity of this mediatory system [87]. Pretreatment with Semax potentiated the effects of D-amphetamine on the dopaminergic system of the striatum and on the locomotor activity of rats. ...
The peptide ACTH4–7-PGP has a wide spectrum of neuroprotective actions, including antioxidant and antidepressant effects in stress conditions. One important question is that of explaining the role of corticosterone in behavioral reactions on the background of repeated administration of ACTH4–7-PGP in chronic stress. The aim of the present work was to study the effects of ACTH4–7-PGP on behavioral reactions and corticosterone levels and their interaction in long-term stress in rats. ACTH4–7-PGP was given to male Wistar rats at doses of 5, 50, 150, and 450 μg/kg for 14 days 12–15 min before imposition of stress. The animals’ behavior was studied in the open field test and the elevated plus maze, and blood corticosterone concentrations were estimated by ELISA. In conditions of chronic stress, peptide was found to have an anxiolytic action and to decrease anxiety levels at doses of 50 and 150 μg/kg (p < 0.05–0.01). All ACTH4–7-PGP doses decreased serum corticosterone concentrations in stressed ats by 28.6–34.2% (p < 0.05). Correlation analysis showed that the decrease in anxiety on administration of ACTH4–7-PGP at a dose of 50 μg/kg had a direct and strong link with the decrease in the corticosterone level.
The effects of peptide ACTH4-7-PGP (Semax) were studied in 12 min after its intraperitoneal (in doses of 5, 15, 50, 150, and 450 μg/kg) or intracerebroventricular (in doses of 16, 40, and 400 pg) administration to rats with different types of pain and pain-induced behavior. It was found that the peptide increased pain sensitivity and induced avoidance behavior during thermal stimulation ("hot plate" test), but had an analgesic effect (more pronounced after central administration) and weakened emotional-affective behavior in electrocutaneous stimulation of the paws (foot-shock model) and tail in rats. It was shown that changes in activity of supraspinal brain structures were of primary importance in the mechanism of action on the nociceptive process and the formation of behavior.
In this review, based on published experimental and clinical data (1980‒2016), a comparative analysis of the structures and effects of Semax (peptide drug) and its analogue fragments was carried out. The effect of these oligopeptides on various body systems is examined. The multiple effects of Semax for a number of diseases have been collected for a single scheme of corrective processes. The rationale for the long-term therapeutic effects of this peptide drug is presented. A comparative analysis of the temporal dynamics of the expression of certain genes is carried out.
Parkinson’s disease (PD) is the second most common severe neurodegenerative disorder that is characterized by progressive degeneration of dopaminergic neurons (DA neurons) in the substantia nigra pars compacta (SNpc) region of the brain. In the present study, we investigated the effects of the synthetic regulatory peptides Semax (analog of an ACTH 4-10 fragment (ACTH4-10)) and Selank (analog of immunomodulatory taftsin) on behavior of rats with 6-hydroxidopamine (6-OHDA) induced PD-like parkinsonism. It was showed that both peptides did not affect motor activity of rats in elevated cross shaped maze and passive defensive behavior of the animals. At the same time, Selank decreased level of anxiety of rats with toxic damage of DA neurons in elevated cross shaped maze. Previously such effects of Selank were revealed in healthy rodents (rats and mice) with different models of psycho-emotional stress. Therefore, toxic damage of substantia nigra does not affect the response of the rat organism on this peptide.
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