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Psychopharmacology

, Volume 121, Issue 3, pp 364–372 | Cite as

The role of the 5-HT2A and 5-HT2C receptors in the stimulus effects of hallucinogenic drugs III: the mechanistic basis for supersensitivity to the LSD stimulus following serotonin depletion

  • D. Fiorella
  • S. Helsley
  • D. S. Lorrain
  • R. A. Rabin
  • J. C. Winter
Original Investigation

Abstract

The present study was designed to determine the effects ofp-chlorophenylalanine (PCPA) andp-chloroamphetamine (PCA) administration on (1) the levels of serotonin (5-hydroxytryptamine, 5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in rat brain, (2) the sensitivity of LSD-trained rats to the stimulus effects of LSD, and (3) the maximal levels of 5-HT2A and 5-HT2C receptor mediated phosphoinositide (PI) hydrolysis in rat brain. PCA and PCPA both produced a significant depletion of whole brain 5-HT and 5-HIAA concentrations. The depletion of serotonin with PCPA, but not PCA, resulted in supersensitivity of LSD-trained subjects to the stimulus effects of LSD. Neither PCPA nor PCA treatment altered the maximal level of 5-HT2A receptor-mediated PI hydrolysis. However, PCPA, but not PCA, treatment resulted in a significant upregulation (46%,P<0.05) of the maximal level of 5-HT2C receptor mediated PI hydrolysis. These data suggest that upregulation of the 5-HT2C receptor mediates the supersensitivity to LSD discriminative stimulus which follows the depletion of central nervous system serotonin by PCPA.

Key words

Serotonin Hallucinogens LSD p-Chloroamphetamine (PCA) p-Chlorophenylalanine (PCPA) Drug-induced stimulus control Phosphoinositide hydrolysis 5-HT2A 5-HT2C 

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Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • D. Fiorella
    • 1
  • S. Helsley
    • 1
  • D. S. Lorrain
    • 1
  • R. A. Rabin
    • 1
  • J. C. Winter
    • 1
  1. 1.Department of Pharmacology and Toxicology, School of Medicine and Biomedical SciencesState University of New York at BuffaloBuffaloUSA

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