Effect of olanzapine on functional responses from sensitized D-1-dopamine receptors in rats with neonatal dopamine loss

Previous work has suggested that the therapeutic efficacy of olanzapine mig ht be partially dependent on action at the D-1-dopamine (DA) receptor site. Because early DA loss can lead to supersensitive D-1-DA receptors, effects of olanzapine were investigated in adult rats given lesions to DA-containi ng neurons as neonates. In these animals, locomotor effects of SKF-38393 (a D-1-DA agonist.) were attenuated by olanzapine, but at doses (5 and 10 mg/ kg) that decreased activity when given alone. Olanzapine prevented inductio n of striatal Fos protein by SKF-38393 and partially attenuated the long-te rm "priming" effect of repeated SKF-38393 treatment. Olanzapine also antago nized the stimulant effects of quinpirole (a D-2-type DA agonist) in animal s lesioned as young adults, at doses lower than those necessary to antagoni ze SKF-35393-induced activity. In addition, olanzapine antagonized apomorph ine-induced self-injurious behavior in neonate-lesioned rats in a dose-rela ted fashion. Attenuation of self-injury in this animal model Suggests that olanzapine should be tested against this symptom in patient populations. [N europsychopharmacology 25:224-233] (C) 2001 American College of Neuropsycho pharmacology. Published by Elsevier Science Inc.