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  The neuronal nitric oxide synthase gene is critically involved in neurobehavioral effects of alcohol

Spanagel, R., Siegmund, S., Cowen, M., Schroff, K., Schumann, G., Fiserova, M., et al. (2002). The neuronal nitric oxide synthase gene is critically involved in neurobehavioral effects of alcohol. Journal of Neuroscience, 22(19), 8676-8683.

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Item Permalink: https://hdl.handle.net/11858/00-001M-0000-000E-A137-6 Version Permalink: https://hdl.handle.net/11858/00-001M-0000-000E-A138-4
Genre: Journal Article
Alternative Title : J. Neurosci.

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 Creators:
Spanagel, R1, Author
Siegmund, S1, Author
Cowen, M1, Author
Schroff, KC1, Author
Schumann, G1, Author
Fiserova, M1, Author
Sillaber, I1, Author
Wellek, S1, Author
Singer, M1, Author
Putzke, J1, Author
Affiliations:
1Max Planck Institute of Psychiatry, Max Planck Society, ou_1607137              

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Free keywords: neuronal nitric oxide synthase; nNOS; nNOS splice variants; knock-out mice; alcohol drinking; taste differences; loss of righting reflex; rapid tolerance; NOS inhibitors
 Abstract: In the present study, we describe a new role of the neuronal nitric oxide synthase (nNOS) gene in the regulation of alcohol drinking behavior. Mice deficient in the nNOS gene (nNOS-/-) and wild-type control mice were submitted to a two-bottle free- choice procedure with either water or increasing concentrations of alcohol (2-16%) for 6 weeks. nNOS-/- mice did not differ in consumption and preference for low alcohol concentrations from wild-type animals; however, nNOS-/- mice consumed sixfold more alcohol from highly concentrated alcohol solutions than wild- type mice. Taste studies with either sucrose or quinine solutions revealed that alcohol intake in nNOS -/- and wild- type mice is associated, at least in part, with sweet solution intake but not with the taste of bitterness. When compared with wild-type mice, the nNOS-/- mice were found to be less sensitive to the sedative effects of ethanol as measured by shorter recovery time from ethanol-induced sleep and did not develop rapid tolerance to ethanol-induced hypothermia, although plasma ethanol concentrations were not significantly different from those of controls. Our findings contrast with previous reports that showed that nonselective NOS inhibitors decrease alcohol consumption. However, because alcohol consumption was suppressed in wild-type as well as nNOS -/- mice by the NOS inhibitor N-G-nitro-L-arginine methyl ester, we conclude that the effect of nonselective NOS inhibitors on alcohol drinking is not mediated by nNOS. Other NOS isoforms, most likely in the periphery or other splice variants of the NOS gene, might contribute to the effect of nonselective NOS inhibitors on alcohol drinking. In summary, the nNOS gene is critically involved in the regulation of neurobehavioral effects of alcoho

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Language(s): eng - English
 Dates: 2002-10-01
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 4077
ISI: 000178246000036
 Degree: -

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Title: Journal of Neuroscience
  Alternative Title : J. Neurosci.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 22 (19) Sequence Number: - Start / End Page: 8676 - 8683 Identifier: ISSN: 0270-6474