title: Increased brain nitric oxide levels following ethanol administration.
abstract: Nitric oxide is a ubiquitous messenger molecule, which at elevated concentrations has been implicated in the pathogenesis of several neurological disorders. Its role in oxidative stress, attributed in particular to the formation of peroxynitrite, proceeds through its high affinity for the superoxide radical. Alcoholism has recently been associated with the induction of oxidative stress, which is generally defined as a shift in equilibrium between pro-oxidant and anti-oxidant species in the direction of the former. Furthermore, its primary metabolite acetaldehyde, has been extensively associated with oxidative damage related toxic effects following alcohol ingestion. The principal objective of this study was the application of long term in vivo electrochemistry (LIVE) to investigate the effect of ethanol (0.125, 0.5 and 2.0 g kg(-1)) and acetaldehyde (12.5, 50 and 200 mg kg(-1)) on NO levels in the nucleus accumbens of freely moving rats. Systemic administrations of ethanol and acetaldehyde resulted in a dose-dependent increases in NO levels, albeit with very differing time courses. Subsequent to this the effect on accumbal NO levels, of subjecting the animal to different drug combinations, was also elucidated. The nitric oxide synthase inhibitor L-NAME (20 mg kg(-1)) and acetaldehyde sequestering agent D-penicillamine (50 mg kg(-1)) both attenuated the increase in NO levels following ethanol (1 g kg(-1)) administration. Conversely, the alcohol dehydrogenase inhibitor 4-methylpyrazole (25 mg kg(-1)) and catalase inhibitor sodium azide (10 mg kg(-1)) potentiated the increase in NO levels following ethanol administration. Finally, dual inhibition of aldehyde dehydrogenase and catalase by cyanamide (25 mg kg(-1)) caused an attenuation of ethanol effects on NO levels. Taken together these data highlight a robust increase in brain NO levels following systemic alcohol administration which is dependent on NO synthase activity and may involve both alcohol- and acetaldehyde-dependent mechanisms.
authors.affiliation: Sensors Development Unit and Neurochemistry Research Unit, BioAnalytics Laboratory, Department of Chemistry, National University of Ireland Maynooth, Maynooth, Ireland.
authors.forename: Niall
authors.initials: N
authors.lastname: Finnerty
authors.affiliation: Sensors Development Unit and Neurochemistry Research Unit, BioAnalytics Laboratory, Department of Chemistry, National University of Ireland Maynooth, Maynooth, Ireland.
authors.forename: Saidhbhe L
authors.initials: SL
authors.lastname: O'Riordan
authors.affiliation: Department of Pharmacology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Klamer
authors.affiliation: Sensors Development Unit and Neurochemistry Research Unit, BioAnalytics Laboratory, Department of Chemistry, National University of Ireland Maynooth, Maynooth, Ireland.
authors.forename: John
authors.initials: J
authors.lastname: Lowry
authors.affiliation: Sensors Development Unit and Neurochemistry Research Unit, BioAnalytics Laboratory, Department of Chemistry, National University of Ireland Maynooth, Maynooth, Ireland; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Electronic address: erik.palsson@neuro.gu.se.
authors.forename: Erik
authors.initials: E
authors.lastname: Pålsson
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D009569:Nitric Oxide; D000431:Ethanol
keywords: Acetaldehyde; Ethanol; Inhibitors; Nitric oxide; Oxidative stress