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P0211 - Increased alcohol sensitivity to stress in mice lacking a functional natriuretic peptide-A receptor

Published online by Cambridge University Press:  16 April 2020

J. Mutschler
Affiliation:
Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany
A. Bilbao
Affiliation:
Department of Psychopharmacology, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany
C.H. von der Goltz
Affiliation:
Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany
H. Jahn
Affiliation:
Department of Psychiatry and Psychotherapie, University of Hamburg, Hamburg, Germany
R. Spanagel
Affiliation:
Department of Psychopharmacology, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany
K. Wiedemann
Affiliation:
Department of Psychiatry and Psychotherapie, University of Hamburg, Hamburg, Germany
F. Kiefer
Affiliation:
Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany

Abstract

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Background:

Recent results suggest that the endocrine system can affect as well as modulate ethanol drinking behavior. In mice and humans a correlation has been found between ANP plasma concentration and craving, anxiety as well as the severity of the withdrawal symptoms. To further elucidate the involvement of the natriuretic peptide system in neurobehavioral effects of alcohol, we examined ethanol drinking behavior in mice lacking a functional natriuretic peptide-A (NPR-A) receptor.

Methods:

NPR-A heterozygote, -knockout and wild-type mice were given a free choice between water and increasing concentrations of ethanol. Once a stable baseline of 16% ethanol consumption was established, access to ethanol was withdrawn for 2 weeks and then reinstated to measure the alcohol deprivation effect (ADE). A forced swim stress was performed thereafter on 3 consecutive days.

Results:

Data analysis revealed a higher ethanol preference and voluntary ethanol intake in NPR-A-transgenic mice. Throughout the experiments the ethanol intake was highest in heterozygote animals. Stress-induced drinking led to an immediate increase in ethanol consumption in the homozygote subgroup. Deprivation from alcohol resulted in a classical ADE in wild-type and heterozygote animals. The homozygote mice do not show an increase in alcohol intake during the ADE.

Conclusions:

We demonstrated that the NPR-A receptor gene is involved in free choice ethanol consumption, preference and ethanol consumption following stress. Mice lacking a functional NPR-A receptor represent a useful animal model to adress the question of whether a dysfunctonal natriuretic peptide receptor system influences longterm alcohol self-administration and stress induced alcohol drinking.

Type
Poster Session II: Depression
Copyright
Copyright © European Psychiatric Association 2008
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