Effects of antipsychotic drugs on extracellular dopamine levels in rat medial prefrontal cortex and nucleus accumbens

Toshihide Kuroki, Herbert Y. Meltzer, Junji Ichikawa

Research output: Contribution to journalArticle

318 Citations (Scopus)

Abstract

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-HT(2A)) and DA-D2 receptors and was inversely correlated to their pKi values for D2 or D3 receptors, but was not for 5- HT(2A) 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-HT(2A) receptor antagonism.

Original languageEnglish
Pages (from-to)774-781
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume288
Issue number2
Publication statusPublished - Feb 1999
Externally publishedYes

Fingerprint

Nucleus Accumbens
Prefrontal Cortex
Antipsychotic Agents
Dopamine
olanzapine
Receptor, Serotonin, 5-HT2A
Serotonin
Sulpiride
Risperidone
Dopamine D2 Receptors
Clozapine
Microdialysis
Haloperidol

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Effects of antipsychotic drugs on extracellular dopamine levels in rat medial prefrontal cortex and nucleus accumbens. / Kuroki, Toshihide; Meltzer, Herbert Y.; Ichikawa, Junji.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 288, No. 2, 02.1999, p. 774-781.

Research output: Contribution to journalArticle

@article{081528d7f6c24ba493c0e1fca59b73b8,
title = "Effects of antipsychotic drugs on extracellular dopamine levels in rat medial prefrontal cortex and nucleus accumbens",
abstract = "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-HT(2A)) and DA-D2 receptors and was inversely correlated to their pKi values for D2 or D3 receptors, but was not for 5- HT(2A) 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-HT(2A) receptor antagonism.",
author = "Toshihide Kuroki and Meltzer, {Herbert Y.} and Junji Ichikawa",
year = "1999",
month = "2",
language = "English",
volume = "288",
pages = "774--781",
journal = "Journal of Pharmacology and Experimental Therapeutics",
issn = "0022-3565",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "2",

}

TY - JOUR

T1 - Effects of antipsychotic drugs on extracellular dopamine levels in rat medial prefrontal cortex and nucleus accumbens

AU - Kuroki, Toshihide

AU - Meltzer, Herbert Y.

AU - Ichikawa, Junji

PY - 1999/2

Y1 - 1999/2

N2 - 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-HT(2A)) and DA-D2 receptors and was inversely correlated to their pKi values for D2 or D3 receptors, but was not for 5- HT(2A) 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-HT(2A) receptor antagonism.

AB - 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-HT(2A)) and DA-D2 receptors and was inversely correlated to their pKi values for D2 or D3 receptors, but was not for 5- HT(2A) 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-HT(2A) receptor antagonism.

UR - http://www.scopus.com/inward/record.url?scp=0033019791&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033019791&partnerID=8YFLogxK

M3 - Article

C2 - 9918588

AN - SCOPUS:0033019791

VL - 288

SP - 774

EP - 781

JO - Journal of Pharmacology and Experimental Therapeutics

JF - Journal of Pharmacology and Experimental Therapeutics

SN - 0022-3565

IS - 2

ER -