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

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.

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.

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.

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.