Central overexpression of angiotensin AT(1A) receptors prevents dopamine D(2) receptor regulation of alcohol consumption in mice.
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.
Moore
Rosanna
R
Howard Florey Institute, University of Melbourne, Parkville, VIC, Australia.
Krstew
Elena V
EV
Kirchhoff
Jeppe
J
Davisson
Robin L
RL
Lawrence
Andrew J
AJ
D000428:Alcohol Drinking / Q000235:genetics / Q000378:metabolism*; D000809:Angiotensins / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001479:Basal Ganglia / Q000187:drug effects* / Q000378:metabolism; D065127:Dopamine D2 Receptor Antagonists; D050483:Dopamine Plasma Membrane Transport Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D004327:Drinking Behavior / Q000187:drug effects / Q000502:physiology; D000431:Ethanol / Q000494:pharmacology; D005440:Fluid Therapy; D005838:Genotype; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D020891:Raclopride / Q000494:pharmacology; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D014882:Water-Electrolyte Balance / Q000187:drug effects
D000809:Angiotensins; D065127:Dopamine D2 Receptor Antagonists; D050483:Dopamine Plasma Membrane Transport Proteins; D044140:Receptor, Angiotensin, Type 1; D017448:Receptors, Dopamine D2; D000431:Ethanol; D020891:Raclopride