Background
Clozapine shows superior efficacy in schizophrenia and enhances prefrontal dopamine
(DA) output like other atypical, but not typical, antipsychotic drugs (APDs). Clinical
data also suggest an improved effect of typical APDs in schizophrenia by adjunctive
treatment with low doses of 3,4-dihydroxyphenylalanine (L-dopa), but experimental
support is scarce, and the underlying mechanisms are poorly understood.
Methods
Antipsychotic efficacy of the D2 antagonist raclopride with or without adjunctive treatment with a low dose of L-dopa
was assessed with the conditioned avoidance response paradigm. Extrapyramidal side
effects were scored by the catalepsy test. Finally, in vivo microdialysis was used
to measure DA efflux in the prefrontal cortex and the nucleus accumbens.
Results
A low dose of L-dopa (3 mg/kg) combined with benserazide, an inhibitor of peripheral
DOPA decarboxylase, significantly enhanced the antipsychotic-like effect of raclopride
without any associated catalepsy. L-dopa/benserazide alone had no effect. In contrast
to raclopride alone, combined L-dopa/raclopride also produced a much larger increase
in DA output in the prefrontal cortex than in the nucleus accumbens.
Conclusions
These data support the clinical observation that low-dose L-dopa might improve the
effect of typical APDs in schizophrenia and indicate that increased prefrontal DA
output per se enhances the antipsychotic effect of typical APDs.
Key Words
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Article info
Publication history
Published online: May 19, 2005
Accepted:
March 23,
2005
Received in revised form:
March 16,
2005
Received:
December 1,
2004
Identification
Copyright
© 2005 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
