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Inhibition of neuronal nitric oxide synthase increases dopamine efflux from rat striatum

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The physiological role of nitric oxide in the control of striatal dopamine release has not been fully established, therefore, the effect of neuronally produced nitric oxide (NO) on striatal dopamine (DA) efflux were investigated using in vivo microdialysis in anaesthetised and conscious rats. In the anaesthetised rat, the nitric oxide synthase inhibitors NG-nitro-L-arginine methylester (L-NAME) and 7-nitroindazole monosodium salt (7-NINA) produced concentration-dependent increases in DA efflux. The L-NAME (1 mM)- and 7-NINA (1 mM)-induced increase was reduced by co-administration with the NO precursor, L-arginine (L-ARG; 1 mM) by 37% and 54% respectively, and was prevented by tetrodotoxin (TTX, 1 μM). Similarly, in conscious rats, L-NAME (1 mM) and 7-NINA (1 mM) increased DA efflux to 161% and 166% of basal efflux respectively. These data suggest that neuronally produced NO inhibits striatal DA efflux through an indirect mechanism.

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Received February 28, 2002; accepted September 24, 2002 Published online December 9, 2002

Acknowledgements This study was supported by the Medical Research Council, the Parkinson's Disease Society and the National Parkinson Foundation, Miami. MTS held a MRC Training Fellowship, SR is a Fellow of the National Parkinson Foundation, Miami.

Authors' address: Prof. P. Jenner, Neurodegenerative Diseases Research Centre, Guy's, King's and St Thomas' School of Biomedical Sciences, King's College London, London, SE1 1UL, United Kingdom, e-mail:

Abbreviations DA dopamine; DOPAC 3,4-dihydroxyphenylacetic acid; HVA homovanillic acid; NO nitric oxide; D-NAME NG-nitro-D-arginine methyl ester; L-NAME NG-nitro-L-arginine methyl ester; NO nitric oxide; MAO-B monoamine oxidase-B; 7-NINA monosodium salt of 7-nitroindazole; NOS nitric oxide synthase

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Silva, M., Rose, S., Hindmarsh, J. et al. Inhibition of neuronal nitric oxide synthase increases dopamine efflux from rat striatum. J Neural Transm 110, 353–362 (2003).

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