Kateryna Murlanova1, Izhak Michaelevski2, Anatoly Kreinin3, Chantelle Terrillion4, Mikhail Pletnikov5, Albert Pinhasov6. 1. Department of Molecular Biology, Ariel University, Ariel 4070000, Israel; Department of Psychiatry and Behavioral Sciences and Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA; Department of Physiology and Biophysics, The Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York 14203, USA. 2. Department of Molecular Biology, Ariel University, Ariel 4070000, Israel; Adelson School of Medicine, Ariel University, Ariel 4070000, Israel. 3. Department of Molecular Biology, Ariel University, Ariel 4070000, Israel. 4. Department of Psychiatry and Behavioral Sciences and Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. 5. Department of Psychiatry and Behavioral Sciences and Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA; Department of Physiology and Biophysics, The Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York 14203, USA. 6. Department of Molecular Biology, Ariel University, Ariel 4070000, Israel; Adelson School of Medicine, Ariel University, Ariel 4070000, Israel. Electronic address: albertpi@ariel.ac.il.
Abstract
BACKGROUND: Dominant-submissive relationships depend upon functionality of the neural circuits involving monoaminergic neurotransmission. Behavioral profiles of selectively bred dominant (Dom) and submissive (Sub) mice have been proposed to mimic hyperthymic- or depressive-like temperaments observed in patients with affective disorders. These mice differentially respond to psychotropic agents and stressful stimuli, however, the mechanisms underlying these differences remain unclear. To address these mechanisms, we analyzed the brain monoamine content and responses to paroxetine (PXT) in Dom and Sub mice. METHODS: The behavioral effects of PXT (3 mg/kg, single injection) were assessed with the Elevated Plus Maze (EPM) and Forced Swim Test (FST). Monoamine tissue content was analyzed by HPLC-ECD. RESULTS: Compared to Dom, Sub mice had decreased levels of serotonin (5-HT) in the brainstem (BS), reduced levels of norepinephrine (NE) in the prefrontal cortex (PFC), hippocampus (HPC), and striatum (STR) and elevated levels of dopamine (DA) in PFC, HPC, STR and BS. In EPM, PXT administration increased locomotion and exploration in Dom mice, with no effect in Sub mice. In FST, PXT disrupted immobility in Dom mice only. The PXT-produced differences in regional monoamine content were strain-dependent and consistent with the behavioral alterations. LIMITATIONS: Chronic PXT treatment, in vivo monoamine assays and sex-dependent analysis were out of the scope of this study and will be performed in the future in order to provide an in-depth evaluation of the neurochemical mechanisms underlying temperament-dependent responses to SSRIs. CONCLUSIONS: Our findings suggest neurochemical mechanisms that underlie temperament-based response to antidepressant treatment.
BACKGROUND: Dominant-submissive relationships depend upon functionality of the neural circuits involving monoaminergic neurotransmission. Behavioral profiles of selectively bred dominant (Dom) and submissive (Sub) mice have been proposed to mimic hyperthymic- or depressive-like temperaments observed in patients with affective disorders. These mice differentially respond to psychotropic agents and stressful stimuli, however, the mechanisms underlying these differences remain unclear. To address these mechanisms, we analyzed the brain monoamine content and responses to paroxetine (PXT) in Dom and Sub mice. METHODS: The behavioral effects of PXT (3 mg/kg, single injection) were assessed with the Elevated Plus Maze (EPM) and Forced Swim Test (FST). Monoamine tissue content was analyzed by HPLC-ECD. RESULTS: Compared to Dom, Sub mice had decreased levels of serotonin (5-HT) in the brainstem (BS), reduced levels of norepinephrine (NE) in the prefrontal cortex (PFC), hippocampus (HPC), and striatum (STR) and elevated levels of dopamine (DA) in PFC, HPC, STR and BS. In EPM, PXT administration increased locomotion and exploration in Dom mice, with no effect in Sub mice. In FST, PXT disrupted immobility in Dom mice only. The PXT-produced differences in regional monoamine content were strain-dependent and consistent with the behavioral alterations. LIMITATIONS: Chronic PXT treatment, in vivo monoamine assays and sex-dependent analysis were out of the scope of this study and will be performed in the future in order to provide an in-depth evaluation of the neurochemical mechanisms underlying temperament-dependent responses to SSRIs. CONCLUSIONS: Our findings suggest neurochemical mechanisms that underlie temperament-based response to antidepressant treatment.
Authors: Neta Gotlieb; Kathryn Wilsterman; Samantha L Finn; Madison F Browne; Savannah R Bever; Eiko Iwakoshi-Ukena; Kazuyoshi Ukena; George E Bentley; Lance J Kriegsfeld Journal: Front Physiol Date: 2022-06-13 Impact factor: 4.755
Authors: Maria Becker; Karin Abaev; Elena Shmerkin; Liza Weinstein-Fudim; Albert Pinhasov; Asher Ornoy Journal: Int J Mol Sci Date: 2022-10-07 Impact factor: 6.208