PT  - JOURNAL ARTICLE
AU  - Frank I. Tarazi
AU  - Ross J. Baldessarini
AU  - Nora S. Kula
AU  - Kehong Zhang
TI  - Long-Term Effects of Olanzapine, Risperidone, and Quetiapine on Ionotropic Glutamate Receptor Types: Implications for Antipsychotic Drug Treatment
AID  - 10.1124/jpet.103.052597
DP  - 2003 Sep 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1145--1151
VI  - 306
IP  - 3
4099  - http://jpet.aspetjournals.org/content/306/3/1145.short
4100  - http://jpet.aspetjournals.org/content/306/3/1145.full
SO  - J Pharmacol Exp Ther2003 Sep 01; 306
AB  - Levels of ionotropic glutamate (Glu) N-methyl-d-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and kainic acid (KA) receptors in rat forebrain regions were compared by quantitative in vitro receptor autoradiography after continuous treatment for 28 days with the atypical antipsychotics olanzapine, risperidone, and quetiapine, or vehicle controls. All three treatments significantly decreased NMDA binding in caudate-putamen (CPu; by 30, 34, and 26%, respectively) but increased AMPA receptor levels in same region (by 22, 30, and 28%). Olanzapine and risperidone, but not quetiapine, also reduced NMDA receptor labeling in hippocampal CA1 (21 and 19%) and CA3 (23 and 22%) regions. KA receptors were unaltered by any treatment in the brain regions examined. These findings suggest that the antipsychotic effects of olanzapine and risperidone may be mediated in part by NMDA receptors in hippocampus, and perhaps AMPA receptors in CPu. The findings also support the hypothesis that down-regulation of NMDA receptors by atypical antipsychotic agents in CPu contributes to their low risk of extra-pyramidal side effects. Inability of olanzapine, risperidone, and quetiapine to alter KA receptors suggests their minimal role in mediating the central nervous system actions of these drugs. The American Society for Pharmacology and Experimental Therapeutics