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Central Overexpression of Angiotensin AT 1A Receptors Prevents Dopamine D 2 Receptor Regulation of Alcohol Consumption in Mice
Author(s) -
Moore Rosanna,
Krstew Elena V.,
Kirchhoff Jeppe,
Davisson Robin L.,
Lawrence Andrew J.
Publication year - 2007
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2007.00399.x
Subject(s) - raclopride , receptor , dopaminergic , endocrinology , medicine , angiotensin ii , dopamine receptor d2 , angiotensin receptor , dopamine , dopamine receptor , biology , chemistry
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 AT 1A receptors (NSE‐AT 1A 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 AT 1A receptors was confirmed by an exaggerated rehydration response following 24‐hour dehydration. NSE‐AT 1A mice showed a high preference for alcohol (similar to wild‐type mice); yet, raclopride treatment had no effect on alcohol consumption in NSE‐AT 1A mice, while significantly reducing consumption in wild‐type mice. In contrast, NSE‐AT 1A mice showed enhanced sensitivity to raclopride compared with wild types in terms of D 2 receptor up‐regulation within the ventral mesencephalon. In addition, striatal D 2 receptors in NSE‐AT 1A mice were sensitive to up‐regulation by chronic alcohol consumption. Conclusions: Collectively, these data imply that while expression of angiotensin AT 1A receptors on striatal neurons has no impact upon basal alcohol consumption or preference, AT 1A receptors do modulate the sensitivity of dopamine D 2 receptors to regulation by alcohol and the ability of a D 2 receptor antagonist to reduce consumption.