Jana Ruda-Kucerova1,2, Petra Amchova1,2, Tereza Havlickova3, Pavel Jerabek3, Zuzana Babinska1,2, Petr Kacer4, Kamila Syslova4, Alexandra Sulcova1, Magdalena Sustkova-Fiserova3. 1. a Experimental and Applied Neuropsychopharmacology Research Group , CEITEC - Central European Institute of Technology, Masaryk University , Brno , Czech Republic . 2. b Department of Pharmacology , Faculty of Medicine, Masaryk University , Brno , Czech Republic . 3. c Department of Pharmacology , Third Faculty of Medicine, Charles University , Prague , Czech Republic , and. 4. d Laboratory of Medicinal Diagnostics, Department of Organic Technology ICT , Prague , Czech Republic.
Abstract
OBJECTIVES: The self-medication hypothesis assumes that symptoms related to potential monoaminergic deficits in depression may be relieved by drug abuse. The aim of this study was to elucidate the neurotransmitter changes in a rat model of depression by measuring their levels in the nucleus accumbens shell, which is typically involved in the drug of abuse acquisition mechanism. METHODS: Depression was modelled by the olfactory bulbectomy (OBX) in Wistar male rats. In vivo microdialysis was performed, starting from the baseline and following after a single methamphetamine injection and behaviour was monitored. The determination of neurotransmitters and their metabolites was performed by high-performance liquid chromatography combined with mass spectrometry. RESULTS: OBX animals had lower basal levels of dopamine and serotonin and their metabolites. However, γ-aminobutyric acid (GABA) and glutamate levels were increased. The methamphetamine injection induced stronger dopamine and serotonin release in the OBX rats and lower release of glutamate in comparison with sham-operated rats; GABA levels did not differ significantly. CONCLUSIONS: This study provides an evidence of mesolimbic neurotransmitter changes in the rat model of depression which may elucidate mechanisms underlying intravenous self-administration studies in which OBX rats were demonstrated to have higher drug intake in comparison to intact controls.
OBJECTIVES: The self-medication hypothesis assumes that symptoms related to potential monoaminergic deficits in depression may be relieved by drug abuse. The aim of this study was to elucidate the neurotransmitter changes in a rat model of depression by measuring their levels in the nucleus accumbens shell, which is typically involved in the drug of abuse acquisition mechanism. METHODS:Depression was modelled by the olfactory bulbectomy (OBX) in Wistar male rats. In vivo microdialysis was performed, starting from the baseline and following after a single methamphetamine injection and behaviour was monitored. The determination of neurotransmitters and their metabolites was performed by high-performance liquid chromatography combined with mass spectrometry. RESULTS: OBX animals had lower basal levels of dopamine and serotonin and their metabolites. However, γ-aminobutyric acid (GABA) and glutamate levels were increased. The methamphetamine injection induced stronger dopamine and serotonin release in the OBX rats and lower release of glutamate in comparison with sham-operated rats; GABA levels did not differ significantly. CONCLUSIONS: This study provides an evidence of mesolimbic neurotransmitter changes in the rat model of depression which may elucidate mechanisms underlying intravenous self-administration studies in which OBX rats were demonstrated to have higher drug intake in comparison to intact controls.
Entities:
Keywords:
Depression; in vivo microdialysis; methamphetamine; olfactory bulbectomy; rats
Authors: Jana Ruda-Kucerova; Mary Tresa Zanda; Petra Amchova; Walter Fratta; Liana Fattore Journal: Front Behav Neurosci Date: 2018-10-30 Impact factor: 3.558