Brain-specific overexpression of angiotensin AT1A receptors in mice modulates the sensitivity of dopamine D2 receptors to regulation by alcohol and the ability of a D2 receptor antagonist to reduce consumption.
AT1A overexpression blunts D2 antagonist effects on alcohol intake in mice; leaves open AT1-D2 interactions as a research target in alcohol use disorder.
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.
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Moore et al. (2007) studied this question.
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