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Repeated antipsychotic drug exposurein developing rats: Dopamine receptor effects
Author(s) -
MoranGates Taylor,
Gan Lu,
Park Young Shik,
Zhang Kehong,
Baldessarini Ross J.,
Tarazi Frank I.
Publication year - 2006
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20220
Subject(s) - olanzapine , clozapine , antipsychotic , dopamine receptor d2 , nucleus accumbens , fluphenazine , atypical antipsychotic , dopamine , medicine , pharmacology , dopamine receptor , psychology , endocrinology , schizophrenia (object oriented programming) , haloperidol , psychiatry
Antipsychotic drugs are often prescribed to juvenile psychiatric patients, though their cerebral effects during development are incompletely described. Accordingly, we studied the effects of repeated treatment with dissimilar antipsychotic drugs on dopamine (DA) receptors in juvenile vs. adult rats. Tissue levels of DA receptor types (D 1 , D 2 , D 3 , and D 4 ) in forebrain regions of juvenile rats were quantified after 3 weeks of daily treatment with representative first‐ (fluphenazine) and second‐generation (clozapine and olanzapine) antipsychotics, and compared with similarly treated adult rats examined in previous studies. Fluphenazine, clozapine, and olanzapine all decreased D 1 receptors in dorsolateral frontal and medial prefrontal cortex (MPC) of juvenile, but not adult rats. Conversely, all three test agents increased D 2 labeling in MPC of adult, but not young animals. Fluphenazine and olanzapine, but not clozapine, also increased D 2 receptor levels in hippocampus, and D 4 levels in nucleus accumbens (NAc) and caudate‐putamen (CPu) in both juvenile and adult brain. D 3 receptors were not altered by any treatment in any brain region at either age. Only some DA receptor adaptations to antipsychotic treatment are shared by developing and mature animals. Developmental differences in DA receptor responses may account for differences in clinical effects of antipsychotic drugs between young and adult psychiatric patients. Synapse 59:92–100, 2006. © 2005 Wiley‐Liss, Inc.