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Alcohol and Alcoholism Vol. 36, No. 1, pp. 65-69, 2001
© 2001 Medical Council on Alcoholism

Expression, but not activity, of neuronal nitric oxide synthase is regionally increased in the alcoholic brain{dagger}

M. Gerlach*, D. Blum-Degen, G. Ransmayr1, F. Leblhuber2, V. Pedersen{ddagger} and P. Riederer

Division of Clinical Neurochemistry and Drug Dependence Unit, University Hospital for Psychiatry, Füchsleinstraße 15, 97080 Würzburg, Germany,
1 Department of Neurology, University of Innsbruck, Anichstraße 35, 6020 Innsbruck and
2 Department of Gerontology, LNK Wagner-Jauregg, Wagner-Jauregg-Weg 15, 4021 Linz, Austria

Received 12 April 2000; in revised form 23 June 2000; accepted 30 June 2000

— The regional distribution of nitric oxide synthase (NOS) was investigated in alcoholic post-mortem brains compared with brains of non-alcoholic control individuals. Total enzyme activity in 28 brain regions was determined using the [3H]l-citrulline formation assay, whereas Western blot analyses were used for semi-quantitative measurement of the neuronal isoform of NOS (nNOS). In the alcoholic brain, nNOS protein expression was increased in the following regions: frontal cortex (85%), the cingulate gyrus (294%), the nucleus accumbens (54%), the entorhinal cortex (85%) and the thalamus (51%). These increases were, however, not associated with higher total NOS activity. Interestingly, nNOS protein content was increased in the frontal cortex and the nucleus accumbens, brain regions which are suggested to be involved in the dopaminergic mesolimbic reward system. It is concluded that upregulation of signal transduction pathways, such as the adenosine 3',5'-monophosphate and the protein kinase C-dependent pathway, due to stimulation of G-protein-coupled neurotransmitter receptor regulation, as a form of functional tolerance, could be responsible for increased nNOS protein expression, and downregulation of NOS enzyme activity in these brain regions.


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