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Long-Term L-DOPA Treatment Causes Indiscriminate Increase in Dopamine Levels at the Cost of Serotonin Synthesis in Discrete Brain Regions of Rats

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Title Long-Term L-DOPA Treatment Causes Indiscriminate
Increase in Dopamine Levels at the Cost of Serotonin
Synthesis in Discrete Brain Regions of Rats
 
Creator Borah, Anupom
Mohanakumar, K P
 
Subject Cell Biology & Physiology
 
Description 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 (250 mg/kg) and carbidopa
(25 mg/kg) daily for 59 and 60 days, and killed on the 60th day, respectively at 24 h and
30 min 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 30 min
after long-term L-DOPA, except in NAc. The cortex and striatum showed lowered levels of
this indoleamine 24 h after 59 doses of L-DOPA. Dopamine, HVA, and DOPAC concentrations
were significantly higher in all the regions studied after 30 min, and in the cerebellum
after 24 h of L-DOPA. The levels of DOPAC were elevated in all the brain areas studied 24 h
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.
 
Date 2007
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/260/1/CELLULAR_AND_MOLECULAR_NEUROBIOLOGY%2C27(8)%2C_985%2D996_%2C2007_[13].pdf
Borah, Anupom and Mohanakumar, K P (2007) Long-Term L-DOPA Treatment Causes Indiscriminate Increase in Dopamine Levels at the Cost of Serotonin Synthesis in Discrete Brain Regions of Rats. Cell Mol Neurobiol, 27 (8). pp. 985-996.
 
Relation http://dx.doi.org/10.1007/s10571-007-9213-6
http://www.eprints.iicb.res.in/260/