Chronic treatment with atypical neuroleptics induces striosomal FosB/ΔFosB expression in rats

Cristina Grande, Hongwen Zhu, Ana B. Martin, Moonsook Lee, Oscar Ortiz, Noboru Hiroi, Rosario Moratalla

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


Background Studies have shown that neuroleptics regulate expression of the transcription factor FosB/ΔFosB 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/ΔFosB 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/ΔFosB were examined. Results Chronic clozapine induced clustered FosB/ΔFosB expression within striosomes of the caudate-putamen. This pattern was due to increased levels of FosB/ΔFosB in striosomes within the ventrolateral caudate-putamen and reduced levels of basal FosB/ΔFosB in the matrix in the entire caudate-putamen. In contrast, chronic haloperidol increased FosB/ΔFosB equally within the matrix and striosomes throughout the entire caudate-putamen. Chronic olanzapine induced an intermediate pattern. Conclusions The relative absence of FosB/ΔFosB expression in the matrix correlates with the lack of parkinsonism of atypical neuroleptics. Expression of FosB/ΔFosB in the matrix may contribute to parkinsonism of typical neuroleptics.

Original languageEnglish (US)
Pages (from-to)457-463
Number of pages7
JournalBiological Psychiatry
Issue number5
StatePublished - Mar 1 2004


  • Extrapyramidal motor side effects
  • FosB
  • Matrix
  • Neuroleptics
  • Schizophrenia
  • Striosome

ASJC Scopus subject areas

  • Biological Psychiatry


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