caa a22 4500 463254708 CHVBK 20180405153351.0 cr unu---uuuuu 170326e20071201xx s 000 0 eng 10.1007/s10571-007-9213-6 doi (NATIONALLICENCE)springer-10.1007/s10571-007-9213-6 Long-Term L-DOPA Treatment Causes Indiscriminate Increase in Dopamine Levels at the Cost of Serotonin Synthesis in Discrete Brain Regions of Rats [Elektronische Daten] [Anupom Borah, Kochupurackal Mohanakumar] (1) The treatment of choice for Parkinson's disease (PD) is 3,4-dihydroxyphenylalanine (L-DOPA) with peripheral decarboxylase inhibitor, but long-term therapy leads to motor and psychiatric complications. In the present study we investigated 5-hydroxytryptamine (5-HT) and dopamine concentrations in serotonergic and dopaminergic nuclei following chronic administration of L-DOPA to find whether the neurotransmitter synthesis in these brain areas are compensated. (2) Rats were administered L-DOPA (250mg/kg) and carbidopa (25mg/kg) daily for 59 and 60days, and killed on the 60th day, respectively at 24h and 30min after the last dose. L-DOPA, norepinephrine, 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), dopamine, homovanillic acid (HVA), and 3,4-dihydroxyphenylacetic acid (DOPAC) were measured in striatum, nucleus raphe dorsalis (NRD), nucleus accumbens (NAc), substantia nigra, cerebellum, and cortex employing HPLC-electrochemical procedure. (3) Prolonged treatment of L-DOPA caused depression in the animals as revealed in a forced swim test. Serotonin content was significantly decreased in all brain regions studied 30min after long-term L-DOPA, except in NAc. The cortex and striatum showed lowered levels of this indoleamine 24h after 59 doses of L-DOPA. Dopamine, HVA, and DOPAC concentrations were significantly higher in all the regions studied after 30min, and in the cerebellum after 24h of L-DOPA. The levels of DOPAC were elevated in all the brain areas studied 24h after prolonged L-DOPA treatment. (4) The present results suggest that long-term L-DOPA treatment results in significant loss of 5-HT in serotonergic and dopaminergic regions of the brain. Furthermore, while L-DOPA metabolism per se was uninfluenced, dopamine synthesis was severely impaired in all the regions. The imbalance of serotonin and dopamine formation may be the cause of overt cognitive, motor, and psychological functional aberrations seen in parkinsonian patients following prolonged L-DOPA treatment. Springer Science+Business Media, LLC, 2007 Parkinson's disease nationallicence Forced swim test nationallicence Dopamine and serotonin synthesis nationallicence Motor behavior nationallicence Nucleus raphe nationallicence Borah Anupom Division of Cell Biology and Physiology, Laboratory of Neuroscience, Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Jadvpur, 700 032, Kolkata, India aut Mohanakumar Kochupurackal Division of Cell Biology and Physiology, Laboratory of Neuroscience, Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Jadvpur, 700 032, Kolkata, India aut Cellular and Molecular Neurobiology Springer US; http://www.springer-ny.com 27/8(2007-12-01), 985-996 0272-4340 27:8<985 2007 27 10571 https://doi.org/10.1007/s10571-007-9213-6 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10571-007-9213-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Borah Anupom Division of Cell Biology and Physiology, Laboratory of Neuroscience, Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Jadvpur, 700 032, Kolkata, India aut NATIONALLICENCE 700 1- Mohanakumar Kochupurackal Division of Cell Biology and Physiology, Laboratory of Neuroscience, Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Jadvpur, 700 032, Kolkata, India aut NATIONALLICENCE 773 0- Cellular and Molecular Neurobiology Springer US; http://www.springer-ny.com 27/8(2007-12-01), 985-996 0272-4340 27:8<985 2007 27 10571 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer