Enhancement of ethanol reward by dopamine D3 receptor blockade

This experiment examined the influence of U-99194A, a dopamine D3 receptor antagonist, on ethanol's rewarding effect in a place conditioning paradigm. Swiss-Webster mice received six pairings of a tactile stimulus with ethanol (2 g/kg, i.p.), U-99194A (20 mg/kg, i. p.) with ethanol, or U-99194A alone. A different stimulus was paired with saline. During conditioning, ethanol or ethanol/U-99194A produced similar increases in locomotor activity. U-99194A alone produced modest increases in activity on some trials. As expected, the 2 g/kg ethanol dose produced a nonsignificant trend towards conditioned place preference. However, U-99194A enhanced the acquisition of ethanol preference, whereas U-99194A alone did not produce either place preference or aversion. The results are consistent with the notion that dopamine D3 systems are important in the response to ethanol and further suggest that D3 receptor blockade increases ethanol reward.