NDLI: Neurochemical Interactions of Competitive N-Methyl-D-Aspartate Antagonists with Dopaminergic Neurotransmission and the Cerebellar Cyclic GMP System: Functional Evidence for a Phasic Glutamatergic Control of the Nigrostriatal Dopaminergic Pathway

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Neurochemical Interactions of Competitive N-Methyl-D-Aspartate Antagonists with Dopaminergic Neurotransmission and the Cerebellar Cyclic GMP System: Functional Evidence for a Phasic Glutamatergic Control of the Nigrostriatal Dopaminergic Pathway

Content Provider	Scilit
Author	Rao, Tadimeti S. Cler, Julie A. Mick, Steve J. Emmett, Mark R. Farah, John M. Contreras, Patricia C. Iyengar, Smriti Wood, Paul L.
Copyright Year	1991
Description	Journal: Journal of Neurochemistry Direct intrastriatal injection of N-methyl-D-aspartate (NMDA; 100 micrograms/rat) increased striatal dopamine (DA) release in vivo. However, parenteral administration of (+/-)-3-(2-carboxypiperizin-4-yl)propyl-1-phosphonic acid (CPP) and cis-4-phosphonomethyl-2-piperidine carboxylic acid (CGS-19755) did not alter DA metabolism and release in several brain regions in the rat and mouse. Intracerebroventricular administration of the competitive NMDA antagonists CPP, CGS-19755, 2-amino-5-phosphonopentanoate, and 2-amino-7-phosphonoheptanoate did not alter rat striatal DA metabolism and release but profoundly reduced cerebellar cyclic GMP (cGMP) levels in the same animals. CPP and CGS-19755 decreased basal cerebellar cGMP levels in the mouse with ED50 values of 6 and 1 mg/kg, i.p., respectively. CPP antagonized the harmaline-induced increases in cGMP levels with an ED50 value of 5.0 mg/kg, i.p. CPP (25 mg/kg, i.p.) also decreased basal cGMP levels in mouse cerebellum for up to 3 h, a result suggesting brain bioavailability and a long duration of NMDA receptor antagonism in vivo. These contrasting patterns suggest that NMDA receptors exert a tonic excitatory tone on the guanine nucleotide signal transduction pathway in the cerebellum while exerting a phasic control over nigrostriatal dopaminergic neurotransmission. These results also indicate that competitive NMDA antagonists, unlike phencyclidine receptor agonists, may not mediate biochemical and behavioral effects via dopaminergic mechanisms.
Related Links	http://onlinelibrary.wiley.com/doi/10.1111/j.1471-4159.1991.tb02007.x/pdf
Ending Page	913
Page Count	7
Starting Page	907
e-ISSN	14714159
DOI	10.1111/j.1471-4159.1991.tb02007.x
Journal	Journal of Neurochemistry
Issue Number	3
Volume Number	56
Language	English
Publisher	Wiley-Blackwell
Publisher Date	1991-03-01
Access Restriction	Open
Subject Keyword	Journal: Journal of Neurochemistry N‐methyl‐d‐aspartate Competitive N‐methyl‐d‐aspartate Antagonists Cerebellar Cyclic Gmp
Content Type	Text
Resource Type	Article

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