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

Biggs, C.S., Fowler, L.J., Whitton, P.S. and Starr, M.S. (1996) NMDA receptor antagonists increase the release of dopamine in the substantia nigra of reserpine-treated rats. European Journal of Pharmacology, 299 (1-3). pp. 83-91. 10.1016/0014-2999(95)00837-3.

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DOI: 10.1016/0014-2999(95)00837-3


crodialysis 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 α-methyl-p-tyrosine (200 mg/kg i.p.) pretreatments. Local infusion of high K+ (100 mM) or L-3,4-dihydroxyphenylalanine (L-DOPA, 10 μM) 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 μM), 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 α-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 could explain the enhancement of L-DOPA's antiparkinsonian activity by these compounds in behavioural experiments.

Item Type:Article
Departments, units and centres:Department of Pharmacology > Department of Pharmacology
ID Code:3130
Journal or Publication Title:European Journal of Pharmacology
Deposited By:Library Staff
Deposited On:27 Apr 2012 17:51
Last Modified:27 Apr 2012 17:51

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