Dopamine D₁ and D₂ receptor subtypes functional regulation in corpus striatum of unilateral rotenone lesioned Parkinson's rat model: effect of serotonin, dopamine and norepinephrine.
Parkinson's disease (PD) is due to widespread degeneration in the central and peripheral nervous systems. The hallmark pathology remains in the dopaminergic striatal insufficiency and degeneration of dopaminergic neurons in the substantia nigra.


OBJECTIVE
The present study analysed the effect of serotonin (5-HT), dopamine, and norepinephrine as treatment on rotenone induced hemi-Parkinson's disease in rats and its role in the regulation of dopamine receptor subtypes in the corpus striatum of the experimental rats.


METHODS
Unilateral stereotaxic single-dose infusions of rotenone were administered to the substantia nigra of adult male Wistar rats. Neurotransmitters serotonin (5-HT), dopamine, and norepinephrine treatments were given to rotenone induced hemi-Parkinson's rats. Dopamine receptor and its subtypes (D₁ and D₂) binding assay were carried out. Gene expression studies of dopamine D₁ and D₂ were carried out using real-time PCR.


RESULTS
Scatchard analysis of dopamine and dopamine D₂ receptor showed a significant increase (P<0.001) and dopamine D₁ receptor showed a significant decrease (P<0.001) in the B(max) in corpus striatum of the PD rats compared to control. These altered parameters were reversed to near control in the serotonin- and norepinephrine-treated PD rats and no change was observed in dopamine-treated PD rats. Real-time PCR results confirmed the receptor data.


CONCLUSIONS
Our results showed that serotonin and norepinephrine functionally reversed in dopamine receptors in rotenone-induced hemi-Parkinson's rat. This has clinical significance in the therapeutic management of PD.
Paul
Jes
J
Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, India.
Nandhu
M S
MS
Kuruvilla
Korah P
KP
Paulose
C S
CS
D000818:Animals; D001549:Benzamides / Q000493:pharmacokinetics; D001552:Benzazepines / Q000493:pharmacokinetics; D002395:Catecholamines / Q000494:pharmacology*; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000493:pharmacokinetics; D065127:Dopamine D2 Receptor Antagonists; D004347:Drug Interactions; D007839:Functional Laterality; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000473:pathology*; D011485:Protein Binding / Q000187:drug effects; D011877:Radionuclide Imaging; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D045442:Rotarod Performance Test; D012402:Rotenone / Q000031:analogs & derivatives; D012701:Serotonin / Q000494:pharmacology; D014316:Tritium / Q000493:pharmacokinetics
D001549:Benzamides; D001552:Benzazepines; D002395:Catecholamines; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C534628:SCH 23390; D012402:Rotenone; D014316:Tritium; C028404:rotenolone; D012701:Serotonin; C030265:nemonapride; D004298:Dopamine; D009638:Norepinephrine