Inhibition of neuronal nitric oxide synthase increases dopamine efflux from rat striatum.
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 N(G)-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 microM). 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.
Silva
M T
MT
Neurodegenerative Diseases Research Centre, Guy's, King's & St Thomas' School of Biomedical Sciences, King's College, London, United Kingdom.
Rose
S
S
Hindmarsh
J G
JG
Jenner
P
P
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D004298:Dopamine