Modulation of dopamine uptake by nitric oxide in cultured mesencephalic neurons

• Published in: Brain research 2008-03, Vol.1198, p.27-33
• Main Authors: Salum, Cristiane, Raisman-Vozari, Rita, Michel, Patrik P, Gomes, Margarete Zanardo, Mitkovski, Miso, Ferrario, Juan E, Ginestet, Laure, Del Bel, Elaine A
• Format: Article
• Language: English
• Subjects: Amphetamine; Amphetamine - pharmacology; Animals; Biological and medical sciences; Biomarkers - metabolism; Cells, Cultured; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Dopamine - metabolism; Dopamine Agonists - pharmacology; Dopamine uptake; Dose-Response Relationship, Drug; Free Radical Scavengers - pharmacology; Fundamental and applied biological sciences. Psychology; Immunofluorescence; Immunohistochemistry; Medical sciences; Mesencephalic cell culture; Mesencephalon - cytology; Mesencephalon - metabolism; Neurology; Neurons - drug effects; Neurons - metabolism; Neuropharmacology; Nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Donors - pharmacology; Nitric Oxide Synthase Type I - metabolism; Nitroprusside - pharmacology; Oxidative Stress - drug effects; Oxidative Stress - physiology; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Rats; Rats, Wistar; Sodium nitroprusside; Substantia Nigra - metabolism; Tyrosine 3-Monooxygenase - metabolism; Vertebrates: nervous system and sense organs
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2007.12.054

Abstract Strong evidence obtained from in vivo and ex-vivo studies suggests the existence of interaction between dopaminergic and nitrergic systems. Some of the observations suggest a possible implication of nitric oxide (NO) in dopamine (DA) uptake mechanism. The present work investigated the interaction between both systems by examining the effect of an NO donor, sodium nitroprusside (SNP), associated with the indirect DA agonist, amphetamine (AMPH) on tritiated DA uptake in cultures of embryonic mesencephalic neurons. Consistent with the literature, both AMPH (1, 3 and 10 μM) and SNP (300 μM and 1 mM) inhibited DA uptake in a dose-dependent manner. In addition, the inhibition of DA uptake by AMPH (1 and 3 μM) was significantly increased by the previous addition of SNP (300 μM). The implication of NO in this interaction was supported by the fact that the free radical scavenger N -acetyl- l -Cysteine (500 μM) significantly increased DA uptake and completely abolished the effect of SNP, leaving unaffected that from AMPH on DA uptake. Further, double-labeling immunohistochemistry showed the presence of tyrosine hydroxylase- (TH, marker for dopaminergic neurons) and neuronal NO synthase- (nNOS, marker for NO containing neurons) expressing neurons in mesencephalic cultures. Some dopaminergic neurons also express nNOS giving further support for a pre-synaptic interaction between both systems. This is the first work demonstrating in mesencephalic cultured neurons a combined effect of an NO donor and an indirect DA agonist on specific DA uptake.