Reward related neurotransmitter changes in a model of depression: An in vivo microdialysis study

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.

Key words:

• Depression
• in vivo microdialysis
• methamphetamine
• olfactory bulbectomy
• rats

Acknowledgements

This work was supported by the project “CEITEC – Central European Institute of Technology” (CZ.1.05/1.1.00/02.0068) from European Regional Development Fund, projects of specific research at the Masaryk University (MUNI/A/0886/2013 and MUNI/A/1116/2014), project PRVOUK P34, “Operational Programme Prague – Competitiveness” (CZ.2.16/3.1.00/22197, CZ.2.16/3.1.00/21537) and “National Programme of Sustainability” (NPU I (LO) MSMT – 34870/2013). The funding has not influenced the process of the paper production including among others the data interpretation and submission. The authors are grateful to Ladislav Dusek for his help with statistical analysis of behavioural data, Jan Jurica and Gabriela Dovrtelova for help with turnover data interpretation and Vanessa Raileanu (Toronto, Canada) for the help with manuscript preparation and proof reading.

Statement of interest

None to declare.