Journal of Molecular Neuroscience

, Volume 38, Issue 3, pp 227–235 | Cite as

Subchronic Effects of Phencyclidine on Dopamine and Serotonin Receptors: Implications for Schizophrenia

  • Yong Kee Choi
  • Shikha Snigdha
  • Mohammed Shahid
  • Jo C. Neill
  • Frank I. Tarazi
Article

Abstract

Changes in representative dopamine (D1, D2, and D4) and serotonin (5-HT1A and 5-HT2A) receptors that have been implicated in the pathophysiology and treatment of schizophrenia were autoradiographically quantified after subchronic phencyclidine (PCP) treatment (2 mg/kg for 7 days, bi-daily followed by 7 days drug free). This treatment has consistently induced robust and long-lasting cognitive deficits in adult rats, although the molecular mechanisms contributing to PCP-induced cognitive deficits remain undefined. Repeated PCP treatment significantly decreased labeling of D1 receptors in the medial and lateral caudate–putamen (22% and 23%, respectively) and increased 5HT1A receptor binding in the medial–prefrontal (26%) and dorsolateral–frontal cortex (30%). No changes in D1 or 5HT1A receptors were detected in other brain regions. These findings suggest that downregulation of striatal D1 receptors and upregulation of cortical 5HT1A receptors may contribute to PCP-induced impairment of cognitive functions in rats. Subchronic PCP treatment did not alter levels of D2, D4, and 5HT2A receptors in all brain regions examined, which suggests a minimal role for these receptors in mediating subchronic actions of PCP in adult rats.

Keywords

Autoradiography Caudate–putamen Cognitive functions Dopamine receptors Frontal cortex Phencyclidine Serotonin receptors 

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Copyright information

© Humana Press 2009

Authors and Affiliations

  • Yong Kee Choi
    • 1
    • 2
  • Shikha Snigdha
    • 3
  • Mohammed Shahid
    • 4
  • Jo C. Neill
    • 3
  • Frank I. Tarazi
    • 1
    • 2
    • 5
  1. 1.Mailman Research CenterMcLean Division of Massachusetts General HospitalBelmontUSA
  2. 2.Department of Psychiatry and Neuroscience ProgramHarvard Medical SchoolBostonUSA
  3. 3.The School of PharmacyUniversity of BradfordWest YorkshireUK
  4. 4.Schering-Plough CorporationLanarkshireUK
  5. 5.Laboratory of Psychiatric Neuroscience, McLean HospitalHarvard Medical SchoolBelmontUSA

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