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Vol. 288, Issue 2, 774-781, February 1999
Department of Psychiatry, Saga Medical School, Nabeshima, Saga,
Japan (T.K.); and
Department of Psychiatry, Psychopharmacology
Division, Vanderbilt University School of Medicine, Nashville,
Tennessee (H.Y.M., J.I.).
The present study was designed to compare the effects of typical and
atypical antipsychotic drugs on extracellular dopamine (DA) levels in
the medial prefrontal cortex (mPFC) and the nucleus accumbens (NAC),
using in vivo microdialysis with dual probe implantation in awake,
freely moving rats. Amperozide (2 and 10 mg/kg), clozapine (5 and 20 mg/kg), and olanzapine (10 mg/kg), all of which are atypical
antipsychotics, produced greater increases in extracellular DA levels
in the mPFC than in the NAC. Olanzapine (1 mg/kg), risperidone (0.1 and
1 mg/kg), also an atypical antipsychotic, and
S-(
)-sulpiride (25 mg/kg), a typical antipsychotic,
produced comparable increases in extracellular DA levels in the mPFC
and the NAC. S-()-sulpiride (10 mg/kg) and haloperidol
(0.1 and 1 mg/kg), another typical antipsychotic, significantly
increased extracellular DA levels in the NAC but not in the mPFC. The
effects of the six antipsychotic drugs to increase extracellular DA
levels in the mPFC relative to those in the NAC was positively
correlated with the difference between their pKi values for serotonin
(5-hydroxytryptamine, 5-HT2A) and DA-D2
receptors and was inversely correlated to their pKi values for
D2 or D3 receptors, but was not for
5-HT2A receptors alone. These results are consistent with
the hypothesis that the ability of antipsychotic drugs to produce a
greater increase in prefrontal compared with NAC extracellular DA
levels may be related, in part, to weak D2 and
D3 receptor affinity relative to 5-HT2A receptor antagonism.
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