Effects of the serotonin(2A/2C) receptor agonist and antagonist on phencyclidine-induced dopamine release in rat medial prefrontal cortex

Toshihide Kuroki, Takeshi Kawahara, Yuji Yonezawa, Nobutada Tashiro

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

1. Systemic administration of PCP (7.5 mg/kg, i.p.) produced a greater increase in extracellular DA levels in the mPFC than in the STR and NAC, as determined by in vivo microdialysis of awake, freely moving rats. Preferential activation by PCP of prefrontal DA neurons may be, at least in part, the basis for the pathophysiology of PCP-induced psychosis as well as schizophrenia. 2. Recent studies suggest a possible involvement of 5-HT(2A) receptors in the pathophysiology and treatment of schizophrenia. This study was designed to examine whether and how 5-HT(2A) receptors modulate PCP-induced DA release in the mPFC. 3. The 5-HT(2A/2C) receptor agonist (±)-DOI (2.5 mg/kg, but not 0.75 mg/kg, i.p.), administered 60 min prior to PCP, significantly attenuated the PCP-induced increase in extracellular DA levels. Pretreatment of the 5-HT(2A/2C) receptor antagonist ritanserin (1.0 and 5.0 mg/kg, i.p.), administered 60 min prior to PCP, did not influence the PCP-induced increase. When administered alone, neither DOI (2.5 mg/kg) nor ritanserin (1.0 mg/kg) affected basal extracellular DA levels in the mPFC. 4. The NMDA receptor antagonist MK-801 (1.0 mg/kg, i.p.) also increased extracellular DA levels in the mPFC, but this effect was unaffected by pretreatment with DOI (2.5 mg/kg). 5. These results suggest that the stimulation of 5-HT(2A/2C) receptors may inhibit DA release in the mPFC when it is facilitated by PCP. Other than the NMDA receptor-mediated mechanism may also be involved in the neurochemical interaction between 5-HT(2A) receptors and PCP in the mPFC.

Original languageEnglish
Pages (from-to)1259-1275
Number of pages17
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Volume23
Issue number7
DOIs
Publication statusPublished - Oct 1 1999
Externally publishedYes

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Biological Psychiatry

Cite this