Augmented stress-induced alcohol drinking and withdrawal in mice lacking functional natriuretic peptide-A receptors.
OBJECTIVE
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.
Mutschler
Jochen
J
Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, University of Heidelberg, J 5, 68159 Mannheim, Germany. jochen.mutschler@zi-mannheim.de
Bilbao
Ainhoa
A
von der Goltz
Christoph
C
Demiralay
Cueneyt
C
Jahn
Holger
H
Wiedemann
Klaus
K
Spanagel
Rainer
R
Kiefer
Falk
F
D000428:Alcohol Drinking / Q000009:adverse effects* / Q000235:genetics; D019973:Alcohol-Related Disorders / Q000235:genetics*; D000818:Animals; D001522:Behavior, Animal; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D017461:Receptors, Atrial Natriuretic Factor / Q000235:genetics*; D013312:Stress, Physiological / Q000235:genetics*; D013375:Substance Withdrawal Syndrome / Q000523:psychology*
D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A