Cocaine sensitization prevents the hypolocomotor effects of high but not low doses of PD 128,907

Abstract In this study we examined the effects of the preferential dopamine D 3 receptor agonist S (+)-(4 aR ,10 bR )-3,4,4 a ,10 b -tetrahydro-4-propyl-2 H ,5 H -[1]benzopyrano-[4,3- b ]-1,4-oxazin-9-ol (PD 128,907) on locomotion in mice sensitized to cocaine. In mice repeatedly treated with saline, PD 128,907 induced hypoactivity over a wide dose range (0.01–40 mg/kg); however, after repeated treatment with 40 mg/kg cocaine, higher doses of PD 128,907 (2.5–40 mg/kg) no longer induced hypoactivity whereas the effects of lower doses (0.01–0.16 mg/kg) were not altered. Because lower doses of PD 128,907 are thought to induce hypoactivity via activation of dopamine D 3 receptors, the present data suggest that, under conditions where cocaine induces marked sensitization to its locomotor effects, the sensitivity of these receptors is not altered. In contrast, because higher doses of PD 128,907 can activate dopamine D 2 receptors, it is conceivable that apparent cross-sensitization to its dopamine D 2 receptor agonist properties is responsible for the lack of hypolocomotor effects at high doses. Overall, the results indicate that altered dopamine D 3 receptor sensitivity does not play an important role in the expression of cocaine-induced sensitization.