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Comparison Between Olanzapine and Haloperidol on Procedural Learning and the Relationship With Striatal D₂ Receptor Occupancy in Schizophrenia

Received September 23, 2002; revised May 28, 2003, accepted October 24, 2003. From the Movement Disorder Unit, CHUM Hôtel-Dieu, and Cognitive Neuroscience Center, UQAM, Canada; the Fernand Seguin Research Center, Hôpital Louis-H. Lafontaine, and Department of Psychiatry, Université de Montréal, Canada; the Department of Nuclear Medicine, Notre Dame, CHUM, Canada. Address correspondence to Dr. Bedard, Cognitive Neuroscience Center, UQAM, P.O. Box 8888, Downtown Station, Montreal, Quebec, H3C 3P8, Canada; bedard.marc-andre{at}uqam.ca (E-mail).

The striatum is known to play a primary role in procedural learning. In this study, the authors simultaneously assessed the effects of two antipsychotic drugs on procedural learning and on striatal dopamine (D₂) receptor occupancy. Twenty-seven patients receiving either olanzapine or haloperidol as antipsychotic medication were assessed with the Computed Visual Tracking Task (CVTT) and Single Photon Emission Computed Tomography (SPECT) following the administration of Iodine ¹²³-IBZM (¹²³I-IBZM), a radioligand with a high affinity and specificity for the D₂ receptors. The results showed poorer procedural learning in the haloperidol-treated patients than in normal control subjects, while no difference could be found between olanzapine-treated patients and normal control subjects. In the haloperidol but not the olanzapine group, significant correlations were found between procedural learning deficits and striatal D₂ receptor occupancy. However, there was no significant difference in D₂ receptor occupancy between olanzapine- and haloperidol-treated patients, and this may be related to the high doses of olanzapine and low doses of haloperidol administered. The authors concluded that: 1) striatal D₂ receptor blockade may alter procedural learning in humans; and 2) olanzapine may have a protective effect on procedural learning, even at doses that produce striatal D₂ receptor occupancy as high as that found with haloperidol. This protective effect of olanzapine may be related to its atypical pharmacological properties.

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