D2 receptors have been studied in relation to therapeutic uses of dopaminergic drugs, and psychomotor stimulant effects [as manifested by decreased prepulse inhibition (PPI) of startle and increased locomotor activity] are hallmark behavioral effects of D2 agonists in rats. Genetic studies with mutant mice might be useful in this line of investigation; however, recent studies suggest that mice differ from rats with respect to D2 agonist effects. Accordingly, we studied a wide range of doses of the D2-like agonist quinelorane (0.0032-5.6 mg/kg) and the D1-like agonist R-6-Br-APB [R(烯)-6-bromo-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide] (0.032-5.6 mg/ kg) in outbred Sprague-Dawley rats, outbred Swiss-Webster mice, and inbred 129X1/SvJ, C57BL/6J, and DBA/2J mice. Whereas the D2 agonist dose-dependently decreased PPI and increased locomotion in rats, neither of these effects was observed in outbred or inbred mice. In contrast, the D1 agonist reduced PPI and increased locomotion in SpragueDawley rats and in Swiss-Webster, 129X1/SvJ, and C57BL/6J mice. Neither agonist decreased PPI in DBA/2J mice, although PPI was increased in this strain by a D2 antagonist. Pretreatment with either the D2 antagonist eticlopride (1 mg/kg) or the D1 antagonist SCH39166 [(溪)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2-(1 mg/kg) prevented the PPI-disruptive effects of quinelorane in rats and R-6-Br-APB in mice, suggesting receptor interactions in both species. In summary, psychomotor stimulant effects of a D2 agonist that were robustly observed in outbred rats were absent in several outbred and inbred strains of mice. These results may have implications for the study of mutant mice to investigate genes involved in psychomotor function in humans.Prepulse inhibition (PPI) of the acoustic startle response is a cross-species phenomenon in which the startle response is reduced when the startling stimulus is preceded by a lowintensity prepulse (Graham, 1975;Hoffman and Ison, 1980). Although abundant literature exists describing the dopamine mechanisms regulating PPI in rats, there are relatively few reports describing comparable studies across different strains of mice. It has been well established in rats that D2-like agonists such as quinpirole, 7-OH-DPAT, and quinelorane reliably disrupt PPI in outbred rats (Peng et al., 1990;Caine et al., 1995;Varty and Higgins, 1998;Swerdlow et al., 2000Swerdlow et al., , 2001b, whereas effects of the D1-like agonists SKF38393 and SKF82958 were more variable and strainspecific (Peng et al., 1990;Wan et al., 1996;Swerdlow et al., 2000Swerdlow et al., , 2001b. However, in inbred C57BL6/J and 129S6/SvEv mice, the D2-like agonist quinpirole did not decrease PPI over a wide dose range (Ralph-Williams et al., 2003), whereas D1-like agonists such as SKF82958, SKF81297, and dihydrexidine robustly decreased PPI in those strains and in a hybrid F2 line of closely related strains (Holmes et al., 2001;Ralph-Williams et al., 2003). Furthermore, the mixed D1/D2 receptor agonis...