NMDA receptor antagonists increase the release of dopamine in the substantia nigra of reserpine-treated rats

European Journal of Pharmacology
C S BiggsM S Starr

Abstract

Microdialysis of the substantia nigra pars reticulata in freely moving rats disclosed a steady release of dopamine and its metabolites which was greatly reduced after reserpine (4 mg/kg s.c.) and alpha-methyl-p-tyrosine (200 mg/kg i.p.) pretreatments. Local infusion of high K+ (100 mM) or L-3,4-dihydroxyphenylalanine (L-DOPA, 10 microM) significantly increased dialysate levels of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC), but not homovanillic acid (HVA) in this model. Intranigral application of the non-competitive NMDA receptor antagonist dizocilpine (150 nM), or the competitive NMDA receptor antagonist R-DL-(E)-2-amino-4-methyl-5-phosphono-3-pentanoate (CGP 40116, 10 microM), via the dialysis probe, did not affect the release of dopamine or its metabolites in intact rats, but further suppressed these releases in reserpine plus alpha-methyl-p-tyrosine-treated animals. When the same amounts of dizocilpine or CGP 40116 were coinfused with L-DOPA, however, they potentiated the recovery of dopamine 12-24 times, and of DOPAC 5-10 times (but not HVA), as well as producing detectable behavioural arousal. The facilitation of dopamine formation from L-DOPA by NMDA receptor antagonists in the substantia nigra pars reticulata co...Continue Reading

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Citations

Jan 1, 1995·Journal of Neural Transmission. Parkinson's Disease and Dementia Section·M S Starr
May 23, 1996·European Journal of Pharmacology·S Kaur, M Starr
Nov 9, 2000·European Journal of Pharmacology·N JonkersY Michotte
Jul 1, 1997·Neuroscience and Biobehavioral Reviews·P S Whitton
Oct 17, 1998·Progress in Neurobiology·W Hauber
Aug 4, 2004·Neuroscience and Biobehavioral Reviews·Albert Adell, Francesc Artigas
Aug 26, 1998·Reviews in the Neurosciences·E BezardC E Gross
Jul 15, 2020·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Maria Teresa Rivera-GarciaBita Moghaddam

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