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Werner, C.* ; Raivich, G.* ; Cowen, M.* ; Strekalova, T.* ; Sillaber, I.* ; Buters, J.T.M. ; Hofmann, F.

Importance of NO/cGMP signalling via cGMP-dependent protein kinase II for controlling emotionality and neurobehavioural effects of alcohol.

Eur. J. Neurosci. 20, 3498-3506 (2004)
DOI
Open Access Green as soon as Postprint is submitted to ZB.
Cyclic GMP is a second messenger for nitric oxide (NO) that acts as a mediator for many different physiological functions. The cGMP-dependent protein kinases (cGKs) mediate cellular signalling induced by NO and cGMP. Here, we explored the localization of cGMP-dependent protein kinase type II (cGKII) in the mouse brain. In situ hybridization revealed high levels of cGKII mRNA in cerebral cortex, thalamic nuclei, hypothalamic nuclei, and in several basal forebrain regions including medial septum, striatum and amygdala. The close link to NO and the distribution pattern of cGKII suggested that this enzyme might be involved in emotional reactions and responses to drugs of abuse. Therefore, cGKII knockout animals (cGKII–/–) were compared with littermate controls in behavioural tests (i) for emotion-linked and (ii) for acute and chronic ethanol responses. Deletion of cGKII did not influence aggressive behaviour but led to enhanced anxiety-like behaviour. In terms of acute responses to ethanol, cGKII–/– mice were hyposensitive to hypnotic doses of ethanol as measured by the loss of righting reflex, without an alteration in their blood alcohol elimination. In a two-bottle free choice test, cGKII–/– mice showed elevated alcohol consumption. No taste differences to sweet solutions were observed compared to control animals. In summary, our data show that cGKII activity modulates anxiety-like behaviour and neurobehavioural effects of alcohol.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords agressivie behaviour; alcohol drinking; anxiety-like behaviour; knockout mice; nitric oxide synthase
ISSN (print) / ISBN 0953-816X
e-ISSN 1460-9568
Journal European Journal of Neuroscience
Quellenangaben Volume: 20, Issue: 12, Pages: 3498-3506 Article Number: , Supplement: ,
Publisher Wiley
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) CCG Environmental Dermatology and Allergology (ILBD-KAU)
Institute of Epidemiology (EPI)