A therapeutic role for melatonin antagonism in experimental models of Parkinson's disease.
To determine the effects of endogenous and exogenous melatonin on experimental models of Parkinson's disease (PD), Sprague-Dawley rats were exposed to intracerebroventricular implants of slow release melatonin, pinealectomy (PX), or constant light (LL) and then injected with central 6-hydroxydopamine (6-OHDA) or i.p. 1-methyl-4-phenyl,1-1,2,3,6-tetrahydropyridine (MPTP). The resulting impairment of motor function and related behavioural impairment were exacerbated by melatonin implantation, while PX and exposure to LL significantly reduced the severity of experimental PD. These results are consistent with previous work highlighting the importance of aberrant amine production in neurological disease and demonstrate that treatments that reduce endogenous melatonin bioavailability can ameliorate experimental PD. Furthermore, these findings illustrate that melatonin is not the universal remedy that it is currently claimed to be, and may pose considerable problems in neurological diseases characterised by dopamine degeneration.
Willis
G L
GL
The Bronowski Institute of Behavioural Neuroscience, Coliban Medical Centre, Kyneton, Victoria, Australia.
Armstrong
S M
SM
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001682:Biological Availability; D001835:Body Weight / Q000187:drug effects / Q000528:radiation effects; D002940:Circadian Rhythm / Q000502:physiology; D004195:Disease Models, Animal; D004409:Dyskinesia, Drug-Induced / Q000628:therapy; D016166:Free Radical Scavengers / Q000494:pharmacology* / Q000528:radiation effects; D008297:Male; D008550:Melatonin / Q000494:pharmacology* / Q000528:radiation effects; D009043:Motor Activity / Q000187:drug effects / Q000528:radiation effects; D016627:Oxidopamine; D010300:Parkinson Disease / Q000628:therapy*; D017440:Photoperiod; D010789:Phototherapy; D010870:Pineal Gland / Q000601:surgery*; D051381:Rats; D017207:Rats, Sprague-Dawley
D016166:Free Radical Scavengers; D016627:Oxidopamine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D008550:Melatonin