Chronic treatment with atypical neuroleptics induces striosomal FosB/DeltaFosB expression in rats.
BACKGROUND
Studies have shown that neuroleptics regulate expression of the transcription factor FosB/DeltaFosB in the striatum, including the accumbens and caudate-putamen; however, the striatum is also divided into another structural dimension, the striosome and matrix compartments. The precise distribution of FosB/DeltaFosB induced by chronic neuroleptics in these striatal compartments is poorly understood.


METHODS
Rats received either single acute injections or chronic injections of clozapine (0 or 20 mg/kg, intraperitoneally [IP]), olanzapine (0 or 5 mg/kg, IP), or haloperidol (0 or 1.5 mg/kg, IP) for 25 days. The levels and compartmental distribution of FosB/DeltaFosB were examined.


RESULTS
Chronic clozapine induced clustered FosB/DeltaFosB expression within striosomes of the caudate-putamen. This pattern was due to increased levels of FosB/DeltaFosB in striosomes within the ventrolateral caudate-putamen and reduced levels of basal FosB/DeltaFosB in the matrix in the entire caudate-putamen. In contrast, chronic haloperidol increased FosB/DeltaFosB equally within the matrix and striosomes throughout the entire caudate-putamen. Chronic olanzapine induced an intermediate pattern.


CONCLUSIONS
The relative absence of FosB/DeltaFosB expression in the matrix correlates with the lack of parkinsonism of atypical neuroleptics. Expression of FosB/DeltaFosB in the matrix may contribute to parkinsonism of typical neuroleptics.
Grande
Cristina
C
Cajal Institute (CG, ABM, OO, RM), Consejo Superior de Investigaciones Científicas, Madrid, Spain.
Zhu
Hongwen
H
Martin
Ana B
AB
Lee
MoonSook
M
Ortiz
Oscar
O
Hiroi
Noboru
N
Moratalla
Rosario
R
D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001569:Benzodiazepines / Q000008:administration & dosage* / Q000009:adverse effects; D002421:Caudate Nucleus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D003024:Clozapine / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D006220:Haloperidol / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D009069:Movement Disorders / Q000209:etiology / Q000378:metabolism; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D000077152:Olanzapine; D010446:Peptide Fragments / Q000187:drug effects / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects* / Q000378:metabolism; D011699:Putamen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution; D014157:Transcription Factors / Q000187:drug effects* / Q000378:metabolism
D014150:Antipsychotic Agents; C483820:Fosb protein, rat; D010446:Peptide Fragments; D016760:Proto-Oncogene Proteins c-fos; D014157:Transcription Factors; D001569:Benzodiazepines; D003024:Clozapine; D006220:Haloperidol; D000077152:Olanzapine