Dopamine D3 receptor mutant and wild-type mice exhibit identical responsesto putative D3 receptor-selective agonists and antagonists

Previous studies using a variety of drugs with different affinities for the dopamine (DA) D3 receptor suggested that this receptor is involved in regu lating motor activity and hypothermia. However, the in vivo selectivity of many of these compounds has been repeatedly questioned. To examine the prec ise roles of the DA D3 receptor in motor activity and hypothermic responses , we used mutant mice lacking the DA D3 receptor to evaluate the in vivo ef fects of several putative D3 receptor-selective agonists and antagonists. U sing automated photocell activity chambers, we observed that the decreases in locomotor activity produced by putative D3 receptor-selective agonists a s well as increases in locomotor activity produced by putative D3 receptor antagonists are identical in D3 receptor mutant and wild-type mice. In addi tion, the hypothermia produced by the putative D3 receptor-selective agonis t PD 128907 is identical in both groups of mice. Based on these findings, w e propose that D3 receptors are unlikely to be involved in these effects an d we caution that the putative D3 ligands that have been used to reach conc lusions regarding the functional roles of D3 receptors lack the necessary i n vivo selectivity to support such conclusions. Synapse 31:210-215, 1999. ( C) 1999 Wiley-Liss, Inc.