Central Overexpression of Angiotensin AT1A Receptors Prevents Dopamine D2 Receptor Regulation of Alcohol Consumption in Mice
Rosanna Moore
Howard Florey Institute, University of Melbourne, Parkville, Vic., Australia
Search for more papers by this authorElena V. Krstew
Howard Florey Institute, University of Melbourne, Parkville, Vic., Australia
Search for more papers by this authorJeppe Kirchhoff
Howard Florey Institute, University of Melbourne, Parkville, Vic., Australia
Search for more papers by this authorRobin L. Davisson
Department of Anatomy & Cell Biology, University of Iowa, Iowa City, Iowa
Search for more papers by this authorAndrew J. Lawrence
Howard Florey Institute, University of Melbourne, Parkville, Vic., Australia
Centre for Neuroscience, University of Melbourne, Parkville, Victoria, Australia
Search for more papers by this authorRosanna Moore
Howard Florey Institute, University of Melbourne, Parkville, Vic., Australia
Search for more papers by this authorElena V. Krstew
Howard Florey Institute, University of Melbourne, Parkville, Vic., Australia
Search for more papers by this authorJeppe Kirchhoff
Howard Florey Institute, University of Melbourne, Parkville, Vic., Australia
Search for more papers by this authorRobin L. Davisson
Department of Anatomy & Cell Biology, University of Iowa, Iowa City, Iowa
Search for more papers by this authorAndrew J. Lawrence
Howard Florey Institute, University of Melbourne, Parkville, Vic., Australia
Centre for Neuroscience, University of Melbourne, Parkville, Victoria, Australia
Search for more papers by this authorAJL is a Senior Research Fellow of the NHMRC, Australia, supported by an NHMRC program grant (236805). RLD is an Established Investigator of the American Heart Association. This work was also supported by grants from the National Institutes of Health to RLD (HL 14388 and HL 63887).
Abstract
Background: While angiotensin receptors are found on the soma and terminals of dopaminergic neurons, controversy surrounds the potential role of angiotensin in alcohol consumption.
Methods: Using a transgenic mouse with a brain-specific overexpression of angiotensin AT1A receptors (NSE-AT1A mice), we have examined the role of angiotensin in alcohol consumption and alcohol-induced regulation of the dopaminergic system.
Results: The functional relevance of the overexpressed AT1A receptors was confirmed by an exaggerated rehydration response following 24-hour dehydration. NSE-AT1A mice showed a high preference for alcohol (similar to wild-type mice); yet, raclopride treatment had no effect on alcohol consumption in NSE-AT1A mice, while significantly reducing consumption in wild-type mice. In contrast, NSE-AT1A mice showed enhanced sensitivity to raclopride compared with wild types in terms of D2 receptor up-regulation within the ventral mesencephalon. In addition, striatal D2 receptors in NSE-AT1A mice were sensitive to up-regulation by chronic alcohol consumption.
Conclusions: Collectively, these data imply that while expression of angiotensin AT1A receptors on striatal neurons has no impact upon basal alcohol consumption or preference, AT1A receptors do modulate the sensitivity of dopamine D2 receptors to regulation by alcohol and the ability of a D2 receptor antagonist to reduce consumption.
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