QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (34) Citing Articles via Google Scholar Google Scholar Articles by Spanagel, R. Articles by Putzke, J. Search for Related Content PubMed PubMed Citation Articles by Spanagel, R. Articles by Putzke, J.

 Previous Article  |  Next Article 

The Journal of Neuroscience, October 1, 2002, 22(19):8676-8683

The Neuronal Nitric Oxide Synthase Gene Is Critically Involved in Neurobehavioral Effects of Alcohol

Rainer Spanagel^{1, 2}, Sören Siegmund^{1, 3}, Michael Cowen¹, Karl-Christian Schroff¹, Gunter Schumann¹, Magdalena Fiserova⁴, Inge Sillaber², Stefan Wellek⁵, Manfred Singer³, and Jörg Putzke⁶

¹ Department of Psychopharmacology, Central Institute of Mental Health (CIMH), University of Heidelberg, 68159 Mannheim, Germany, ² Drug Abuse Research Group, Max Planck Institute of Psychiatry, 80804 Munich, Germany, ³ Department of Medicine IV, University Hospital of Heidelberg, 68167 Mannheim, Germany, ⁴ Institute of Pharmacology, Charles University, 10000 Prague, Czech Republic, ⁵ Department of Biostatistics, CIMH, 68159 Mannheim, Germany, and ⁶ Department of Medical Neurobiology, University of Magdeburg, 39120 Magdeburg, Germany

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 alcohol.

Key words: neuronal nitric oxide synthase; nNOS; nNOS splice variants; knock-out mice; alcohol drinking; taste differences; loss of righting reflex; rapid tolerance; NOS inhibitors

---

Copyright © 2002 Society for Neuroscience  0270-6474/02/22198676-08$05.00/0

This article has been cited by other articles:

				G. Schumann, M. Johann, J. Frank, U. Preuss, N. Dahmen, M. Laucht, M. Rietschel, D. Rujescu, A. Lourdusamy, T.-K. Clarke, et al. Systematic Analysis of Glutamatergic Neurotransmission Genes in Alcohol Dependence and Adolescent Risky Drinking Behavior Arch Gen Psychiatry, July 1, 2008; 65(7): 826 - 838. [Abstract] [Full Text] [PDF]

				F. Hofmann, R. Feil, T. Kleppisch, and J. Schlossmann Function of cGMP-Dependent Protein Kinases as Revealed by Gene Deletion Physiol Rev, January 1, 2006; 86(1): 1 - 23. [Abstract] [Full Text] [PDF]

				J. W. Maas Jr, S. K. Vogt, G. C. K. Chan, V. V. Pineda, D. R. Storm, and L. J. Muglia Calcium-Stimulated Adenylyl Cyclases Are Critical Modulators of Neuronal Ethanol Sensitivity J. Neurosci., April 20, 2005; 25(16): 4118 - 4126. [Abstract] [Full Text] [PDF]

				P. M. Newton, C. J. Orr, M. J. Wallace, C. Kim, H.-S. Shin, and R. O. Messing Deletion of N-Type Calcium Channels Alters Ethanol Reward and Reduces Ethanol Consumption in Mice J. Neurosci., November 3, 2004; 24(44): 9862 - 9869. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help