TY - JOUR

T1 - BEHAVIORAL AND NEUROCHEMICAL CHANGES DURING INTRANASAL ADMINISTRATION OF ALPHA-GLUTAMYL-TRYPTOPHAN AND CHELATE COMPLEX OF ZINC ARGINYL-GLYCINATE ON MONOAMINE SYSTEMS DYSFUNCTIONS KNOCK-OUT MODELS

AU - Апрятин, Сергей Алексеевич

AU - Лопачев, Александр Васильевич

AU - Жуков, Илья Сергеевич

AU - Ефимова, Евгения Викторовна

AU - Апрятина, Вера Анатольевна

N1 - Apryatin S, Lopachev A, Zhukov I, Efimova E, Apryatina V. BEHAVIORAL AND NEUROCHEMICAL CHANGES DURING INTRANASAL ADMINISTRATION OF ALPHA-GLUTAMYL-TRYPTOPHAN AND CHELATE COMPLEX OF ZINC ARGINYL-GLYCINATE ON MONOAMINE SYSTEMS DYSFUNCTIONS KNOCK-OUT MODELS. Georgian Med News. 2024 May;(350):73-81. PMID: 39089275.

PY - 2024/5/1

Y1 - 2024/5/1

N2 - Monoamine neurotransmitter system dysfunctions lead to behavioral disorders, cognitive metabolic, and other pathological conditions. In this case, different amino acids are precursors of monoamines, while the parenteral path of monoamine administration has pharmacological restrictions. Therefore, intranasal administration one of the most promising methods of delivering an active substance is. The purpose of the work is to study the effect of intranasal administration of a chelate complex of zinc arginyl-glycinate and alpha-glutamyl-tryptophan dipeptide on behavioral and neurochemical changes in acute and chronic experiments.Material and methods: The studies used outbred Wistar and DAT-KO rats, and inbred C57Bl6 and TAAR1-KO mice. Using intranasal administration of a chelate complex of zinc arginyl-glycinate and alpha-glutamyl-tryptophan dipeptide we tested methods for evaluating different behavioral indicators and the level of cerebral monoamines and their metabolites.Results: An anxiolytic effect of zinc arginyl-glycinate and its combination with alpha-glutamyl-tryptophan was revealed. Both drugs have a physiological effect on the autonomic nervous system, but the determination of their operating mechanisms requires further research.Conclusion: Thus, these data indicate that intranasal delivery of the dipeptides is effective during acute and chronic intranasal administration in rodents, the latter showed a change in the anxiety indicator. Acute AG intranasal administration demonstrated signs of lower anxiety and depressive-like behavior in C57Bl6 mice. The acute intranasal administration of a chelate complex zinc arginyl-glycinate and combination with alpha-glutamyl-tryptophan in doses of 50-100 mg/kg of body weight may be used for pre-clinical studies as a new anxiolytic/antidepressant.

AB - Monoamine neurotransmitter system dysfunctions lead to behavioral disorders, cognitive metabolic, and other pathological conditions. In this case, different amino acids are precursors of monoamines, while the parenteral path of monoamine administration has pharmacological restrictions. Therefore, intranasal administration one of the most promising methods of delivering an active substance is. The purpose of the work is to study the effect of intranasal administration of a chelate complex of zinc arginyl-glycinate and alpha-glutamyl-tryptophan dipeptide on behavioral and neurochemical changes in acute and chronic experiments.Material and methods: The studies used outbred Wistar and DAT-KO rats, and inbred C57Bl6 and TAAR1-KO mice. Using intranasal administration of a chelate complex of zinc arginyl-glycinate and alpha-glutamyl-tryptophan dipeptide we tested methods for evaluating different behavioral indicators and the level of cerebral monoamines and their metabolites.Results: An anxiolytic effect of zinc arginyl-glycinate and its combination with alpha-glutamyl-tryptophan was revealed. Both drugs have a physiological effect on the autonomic nervous system, but the determination of their operating mechanisms requires further research.Conclusion: Thus, these data indicate that intranasal delivery of the dipeptides is effective during acute and chronic intranasal administration in rodents, the latter showed a change in the anxiety indicator. Acute AG intranasal administration demonstrated signs of lower anxiety and depressive-like behavior in C57Bl6 mice. The acute intranasal administration of a chelate complex zinc arginyl-glycinate and combination with alpha-glutamyl-tryptophan in doses of 50-100 mg/kg of body weight may be used for pre-clinical studies as a new anxiolytic/antidepressant.

KW - Administration, Intranasal

KW - Animals

KW - Anti-Anxiety Agents/administration & dosage

KW - Anxiety/drug therapy

KW - Behavior, Animal/drug effects

KW - Biogenic Monoamines/metabolism

KW - Chelating Agents/administration & dosage

KW - Dipeptides/administration & dosage

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Rats

KW - Rats, Wistar

KW - Zinc/administration & dosage

M3 - Article

C2 - 39089275

VL - 5

SP - 73

EP - 81

JO - Georgian medical news

JF - Georgian medical news

SN - 1512-0112

IS - 350

ER -