Age-related differences in MK-801 induced behaviors in dopamine D3 receptor knock out mice

It is not known if age plays an important role in the D(3) receptor regulation of N-methyl-D-aspartate (NMDA) receptor antagonist induced hyperactivity. Wild type (WT) and dopamine D(3) receptor mutant (D(3)R KO) mice were divided into young (under 7 months) and middle age (over 12 months) groups and tested for dizocilpine (MK-801)-induced hyperactivity and rearing. Mice were administered vehicle (saline, 1 ml/100g body weight, i.p.), or dopamine D(3) receptor preferring antagonists 3aR,9bS)-N[4-(8-cyano-1,3a,4,9b-tetrahydro-3H-benzopyrano[3,4-c]pyrrole-2-yl)-butyl] (4-phenyl) benzamide) (S33084, 1.0mg/kg, i.p.) and 5,6-dimethoxy-2(dipropylamino)indan (U99194A, 5.0 mg/kg i.p.), and immediately placed into the open field apparatus. Horizontal and vertical activity counts were recorded for 30 min, followed by injection of vehicle or MK801 (0.15 or 0.30 mg/kg i.p.) and mice returned to the open field for an additional 55 min. Young D(3)R KO mice showed the highest level of locomotor and rearing activity during the 1st 30 min and 2nd 55 min session after vehicle treatment. At the lower dose of MK-801 horizontal activity was significantly higher in Young-D(3)R KO mice than in the other groups. At the higher dose of MK-801 horizontal activity was elevated to an equal extent in all groups. In response to S33084 and U99194A, MK-801 hyperactivity was reduced the most in the Middle Age-D(3)R KO and the least in the Young-D(3)R KO mice. Rearing showed pronounced age-related but not genotype effects. The results demonstrate that MK-801 induced-hyperactivity, novelty-induced behavioral activity and rearing are affected by age and D(3) receptor genotype.