Vadim Tseilikman1, Maria Komelkova2, Maxim Lapshin2, Anatoli Alliluev2, Olga Tseilikman3, Marina Karpenko4, Nina Pestereva4, Eugenia Manukhina5, H Fred Downey6, Marina Kondashevskaya7, Alexey Sarapultsev8, Eliyahu Dremencov9. 1. School of Medical Biology, South Ural State University, Chelyabinsk, Russia. Electronic address: vadimed@yandex.ru. 2. School of Medical Biology, South Ural State University, Chelyabinsk, Russia. 3. School of Medical Biology, South Ural State University, Chelyabinsk, Russia; Faculty of Fundamental Medicine, Chelyabinsk State University, Chelyabinsk, Russia. 4. Institute of Experimental Medicine, Saint Petersburg, Russia. 5. Institute of General Pathology and Pathophysiology, Moscow, Russia; University of North Texas Health Science Center, Fort Worth, Texas, USA. 6. University of North Texas Health Science Center, Fort Worth, Texas, USA. 7. FSBSI Research Institute of Human Morphology, Moscow, Russia. 8. Institute of Immunology and Physiology (IIP) of the Ural Division of Russian Academy of Sciences, Yekaterinburg, Russia. 9. School of Medical Biology, South Ural State University, Chelyabinsk, Russia; Institute of Molecular Physiology and Genetics, Center for Biosciences, Slovak Academy of Sciences, Bratislava, Slovakia; Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia.
Abstract
BACKGROUND: Repeated exposure to predator scent stress (PSS) has been used as an animal model of complex post-traumatic stress disorder (CPTSD). The aim of the current study was to assess brain monoamines and their primary metabolites concentrations in male Wistar rats (16 control, 19 exposed to chronic PSS). METHODS: Rats were exposed to PSS for ten days. Fourteen days later, the rats' anxiety index (AI) was assessed with an elevated plus maze test; based on differences in AI, the rats were segregated into low- (AI ≤ 0.8, n = 9) and high- (AI > 0.8, n = 10) anxiety phenotypes. Plasma corticosterone levels were measured by radioimmunoassay. Brain monoamines and their metabolites were measured using high-performance liquid chromatography with electrochemical detector. RESULTS: PSS exposure led to a significant increase in average rats' AI and a reduction in plasma corticosterone levels. Medullar catecholamines and hippocampal and neocortical norepinephrine levels were increased, and pontine norepinephrine and cerebellar dopamine decreased in PSS-exposed rats. Cerebellar norepinephrine levels were increased, and midbrain, hippocampal, and neocortical 5-HT and hypothalamic and hippocampal dopamine levels-decreased in high-, but not in low-anxiety rats. The decrease in hippocampal dopamine levels was accompanied by an increase of DOPAC levels, suggesting and abnormal metabolism of this transmitter. CONCLUSION: Reductions in 5-HT and dopamine in mid- and forebrain brain areas are associated with stress susceptibility in rodents and perhaps also with PTSD vulnerability in humans. Dopamine and 5-HT metabolism and its modulation by glucocorticoids appear to play a role in stress susceptibility and in CPTSD.
BACKGROUND: Repeated exposure to predator scent stress (PSS) has been used as an animal model of complex post-traumatic stress disorder (CPTSD). The aim of the current study was to assess brain monoamines and their primary metabolites concentrations in male Wistar rats (16 control, 19 exposed to chronic PSS). METHODS:Rats were exposed to PSS for ten days. Fourteen days later, the rats' anxiety index (AI) was assessed with an elevated plus maze test; based on differences in AI, the rats were segregated into low- (AI ≤ 0.8, n = 9) and high- (AI > 0.8, n = 10) anxiety phenotypes. Plasma corticosterone levels were measured by radioimmunoassay. Brain monoamines and their metabolites were measured using high-performance liquid chromatography with electrochemical detector. RESULTS:PSS exposure led to a significant increase in average rats' AI and a reduction in plasma corticosterone levels. Medullar catecholamines and hippocampal and neocortical norepinephrine levels were increased, and pontine norepinephrine and cerebellar dopamine decreased in PSS-exposed rats. Cerebellar norepinephrine levels were increased, and midbrain, hippocampal, and neocortical 5-HT and hypothalamic and hippocampal dopamine levels-decreased in high-, but not in low-anxietyrats. The decrease in hippocampal dopamine levels was accompanied by an increase of DOPAC levels, suggesting and abnormal metabolism of this transmitter. CONCLUSION: Reductions in 5-HT and dopamine in mid- and forebrain brain areas are associated with stress susceptibility in rodents and perhaps also with PTSD vulnerability in humans. Dopamine and 5-HT metabolism and its modulation by glucocorticoids appear to play a role in stress susceptibility and in CPTSD.
Authors: Alexander S Zubov; Irina S Ivleva; Nina S Pestereva; Tatiana V Tiutiunnik; Dmitrtii S Traktirov; Marina N Karpenko Journal: Psychopharmacology (Berl) Date: 2022-05-11 Impact factor: 4.415
Authors: Vadim Tseilikman; Maxim Lapshin; Igor Klebanov; George Chrousos; Maria Vasilieva; Anton Pashkov; Julia Fedotova; David Tseilikman; Vladislav Shatilov; Eugenia Manukhina; Olga Tseilikman; Alexey Sarapultsev; H Fred Downey Journal: Int J Mol Sci Date: 2022-04-28 Impact factor: 6.208
Authors: Maria Komelkova; Eugenia Manukhina; H Fred Downey; Alexey Sarapultsev; Olga Cherkasova; Viacheslav Kotomtsev; Pavel Platkovskiy; Stanislav Fedorov; Petr Sarapultsev; Olga Tseilikman; David Tseilikman; Vadim Tseilikman Journal: Int J Mol Sci Date: 2020-08-17 Impact factor: 5.923
Authors: M V Kondashevskaya; K A Artem'yeva; V V Aleksankina; D A Areshidze; M A Kozlova; L A Makartseva Journal: J Evol Biochem Physiol Date: 2022-08-28 Impact factor: 1.621