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 journalArticle

41 Citations (Scopus)

Abstract

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
Volume55
Issue number5
DOIs
StatePublished - Mar 1 2004

Fingerprint

Putamen
Antipsychotic Agents
olanzapine
Clozapine
Parkinsonian Disorders
Haloperidol
Therapeutics
Corpus Striatum
Injections
Transcription Factors

Keywords

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

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Grande, C., Zhu, H., Martin, A. B., Lee, M., Ortiz, O., Hiroi, N., & Moratalla, R. (2004). Chronic treatment with atypical neuroleptics induces striosomal FosB/ΔFosB expression in rats. Biological Psychiatry, 55(5), 457-463. https://doi.org/10.1016/j.biopsych.2003.08.008

Chronic treatment with atypical neuroleptics induces striosomal FosB/ΔFosB expression in rats. / Grande, Cristina; Zhu, Hongwen; Martin, Ana B.; Lee, Moonsook; Ortiz, Oscar; Hiroi, Noboru; Moratalla, Rosario.

In: Biological Psychiatry, Vol. 55, No. 5, 01.03.2004, p. 457-463.

Research output: Contribution to journalArticle

Grande, C, Zhu, H, Martin, AB, Lee, M, Ortiz, O, Hiroi, N & Moratalla, R 2004, 'Chronic treatment with atypical neuroleptics induces striosomal FosB/ΔFosB expression in rats', Biological Psychiatry, vol. 55, no. 5, pp. 457-463. https://doi.org/10.1016/j.biopsych.2003.08.008
Grande, Cristina ; Zhu, Hongwen ; Martin, Ana B. ; Lee, Moonsook ; Ortiz, Oscar ; Hiroi, Noboru ; Moratalla, Rosario. / Chronic treatment with atypical neuroleptics induces striosomal FosB/ΔFosB expression in rats. In: Biological Psychiatry. 2004 ; Vol. 55, No. 5. pp. 457-463.
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N2 - 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.

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