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Alcohol and Alcoholism

Year: 2010  |  Volume: 45  |  Issue: 1  |  Page No.: 13 - 16

Augmented Stress-Induced Alcohol Drinking and Withdrawal in Mice Lacking Functional Natriuretic Peptide-A Receptors

J Mutschler, A Bilbao, C von der Goltz, C Demiralay, H Jahn, K Wiedemann, R Spanagel and F. Kiefer

Abstract

Aims: Preclinical and clinical data suggest an involvement of atrial natriuretic peptides (ANP) in alcohol-associated psychopathology. We now present first data on alcohol drinking behaviour in mice lacking a functional natriuretic peptide-A (NPR-A) receptor. Methods: NPR-A–/– and wild-type mice were given a free choice between water and increasing concentrations of alcohol (2–16%). A forced swim stress was performed thereafter on three consecutive days to investigate stress-induced alcohol drinking. Additionally, neurobehavioural alcohol withdrawal response was investigated following 14 days of forced-alcohol intake. Results: Whereas basal alcohol intake did not differ between NPR-A mutants and wild-type littermates, NPR-A mutants showed an increased stress-induced alcohol intake and aggravated neurobehavioural symptoms of alcohol withdrawal. Conclusions: Mice lacking a functional NPR-A receptor represent a useful model to study the role of the ANP system in alcohol-associated pathology. To study the role of the natriuretic NPR-A gene for the modulation of risk of alcohol-related disorders, NPR-A-related polymorphisms should be targeted in clinical studies.

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