Destruction of noradrenergic terminals increases dopamine concentration and reduces dopamine metabolism in the medial prefrontal cortex
Autor: | Tamás Ollmann, Anita Kovács, Veronika Kállai, Attila Toth, Beáta Berta, László Péczely, Zoltán Petykó, Rita Gálosi, László Lénárd |
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Rok vydání: | 2018 |
Předmět: |
Male
0301 basic medicine medicine.medical_specialty Microdialysis 3 4-Dihydroxyphenylacetic acid Dopamine Prefrontal Cortex Piperazines Lesion Norepinephrine 03 medical and health sciences Behavioral Neuroscience chemistry.chemical_compound 0302 clinical medicine Dopamine Uptake Inhibitors Internal medicine Neural Pathways medicine Extracellular Animals Rats Wistar Oxidopamine Neurons Yohimbine Adrenergic alpha-2 Receptor Antagonists GBR-12935 Dihydroxyphenylalanine 030104 developmental biology Endocrinology nervous system chemistry 3 4-Dihydroxyphenylacetic Acid medicine.symptom Extracellular Space 030217 neurology & neurosurgery medicine.drug |
Zdroj: | Behavioural Brain Research. 344:57-64 |
ISSN: | 0166-4328 |
DOI: | 10.1016/j.bbr.2018.02.016 |
Popis: | Effects of destroyed noradrenergic (NE) innervation in the medial prefrontal cortex (mPFC) were examined on dopamine (DA) content and metabolism. Six-hydroxy-DOPA (6-OHDOPA) or 6-hydroxy-dopamine (6-OHDA) in combination with a potent DA reuptake inhibitor GBR 12935 or 6-OHDA were injected bilaterally into the mPFC in separate groups of animals. In addition, GBR 12935 or vehicle was injected into the mPFC in two other groups of animals as control experiments. NE and DA concentrations from postmortem tissue of the mPFC were measured using HPLC with electrochemical detection. In addition, extracellular NE, DA and DOPAC levels were determined using in vivo microdialysis after the 6-OHDA lesion in combination with GBR 12935 pretreatment in the mPFC. Using reverse microdialysis of alpha-2-adrenoreceptor antagonist yohimbine, we tested the remaining activity of NE innervation and the extracellular concentration of DA and DOPAC. NE and DA concentrations from postmortem tissue of the mPFC showed that 6-OHDOPA lesion reduced NE concentration to 76%, which was a non-significant alteration, however it enhanced significantly DA concentration to 186% compared to vehicle. After 6-OHDA lesion with GBR 12935 pretreatment, concentration of NE significantly decreased to 51% and DA level increased to 180%. 6-OHDA lesion without GBR 12635 pretreatment decreased NE concentration to 23% and DA concentration to 67%. In the microdialysis experiment, after 6-OHDA lesion with GBR 12935 pretreatment, extracellular NE levels were not detectable, whereas extracellular DA levels were increased and DOPAC levels were decreased compared to controls. Reverse microdialysis of yohimbine demonstrated that the residual NE innervation was able to increase NE level and DA levels, but DOPAC concentration remained low after lesion of the NE terminals. These findings suggest that the damage of NE innervation in the mPFC may alter extracellular DA level due to a reduced DA clearance. |
Databáze: | OpenAIRE |
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