Genotypic differences in brain dopamine receptor function in the DBA/2J and C57BL/6J inbred mouse strains

Area of Science:

• Neuroscience
• Genetics
• Pharmacology

Background:

• Ethanol abuse may stem from congenital deficits in central dopaminergic activity.
• Inbred mouse strains (DBA/2J and C57BL/6J) exhibit differing ethanol preference and consumption.

Purpose of the Study:

• To investigate the role of dopamine D1 and D2 receptor function in ethanol preference and consumption.
• To examine strain-specific differences in dopaminergic activity between DBA/2J and C57BL/6J mice.

Main Methods:

• Compared dopamine D1 and D2 receptor mRNA abundance and density in various brain regions of DBA/2J and C57BL/6J mice.
• Assessed dopamine-sensitive adenylyl cyclase activity and dopamine D2 receptor mRNA regulation following dopamine D1 receptor blockade.

Main Results:

• C57BL/6J mice showed higher forebrain dopamine D1/D2 receptor mRNA and density, and higher striatal dopamine-sensitive adenylyl cyclase activity compared to DBA/2J mice.
• Differences in dopamine D2 receptor mRNA and density were observed in the mesencephalon, hind brain, and diencephalon between strains.
• Ethanol intake increased central dopamine pathway activity in both mouse strains, indicating a link between dopamine receptor function and ethanol consumption.

Conclusions:

• Genetically determined differences in dopamine D1 and D2 receptor mechanisms may contribute to ethanol abuse risk.
• The C57BL/6J mouse strain exhibits specific dopaminergic system characteristics potentially linked to higher ethanol preference.