MK-801 reverses Fos expression induced by the full dopamine D1 receptor agonist SKF-82958 in the rat striatum.

Administration of the selective and full dopamine D1 receptor agonist SKF-82958 ((+/-)-6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-b enzazepine) (1 and 3 mg/kg i.p.) led to a dose-dependent induction of Fos protein in the rat striatum. The 3 mg/kg SKF-82958-induced expression of striatal Fos protein was blocked by the dopamine D1 receptor antagonist SCH-23390 (R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benza zepine) (0.3 mg/kg i.p.). The noncompetitive NMDA receptor antagonist MK-801 ((5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5 ,10-imine) (1 mg/kg i.p.) also completely prevented striatal Fos induction by an injection of 3 mg/kg SKF-82958. These results suggest that dopamine D1 receptor activation by the full agonist SKF-82958 is sufficient to trigger Fos expression in the striatum, but that concomitant stimulation of NMDA receptors is required for the striatal Fos induction in response to dopamine D1 receptor activation.