Psychomotor stimulation by dopamine D₁-like but not D₂-like agonists in most mouse strains

Many neurological and psychiatric disorders are treated with dopamine modulators. Studies in mice may reveal genetic factors underlying those disorders or responsiveness to various treatments, and species and strain differences both complicate the use of mice and provide valuable tools. We evaluated psychomotor effects of the dopamine D₁-like agonist R-6-Br-APB and the dopamine D₂-like agonist quinelorane using a locomotor activity procedure in 15 mouse strains (inbred 129S1/SvImJ, 129S6/SvEvTac, 129X1/SvJ, A/J, BALB/cByJ, BALB/cJ, C3H/HeJ, C57BL/6J, CAST/EiJ, DBA/2J, FVB/NJ, SJL/J, SPRET/EiJ, outbred Swiss Webster, and CD-1) and Sprague-Dawley rats, using groups of both females and males. Both D₁ and D₂ stimulation produced hyperactivity in the rats, and surprisingly, only two mouse strains were similar in that regard (C3H/HeJ, SPRET/EiJ). In contrast, the majority of mouse strains exhibited hyperactivity only with D₁ stimulation, whereas D₂ stimulation had no effect or decreased activity. BALB substrains, A/J and FVB/NJ mice showed only decreased activity after either D₁ or D₂ stimulation. CAST/EiJ mice exhibited hyperactivity exclusively with D₂ stimulation. Sex differences were observed but no systematic trend emerged: For example, of the five strains in which a main factor of sex was identified for the stimulant effects of the D₁ agonist, responsiveness was greatest in females in three of those strains and in males in two of those strains. These results should aid in the selection of mouse strains for future studies in which D₁ or D₂ responsiveness is a necessary consideration in the experimental design.