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.
David Fiorella, Scott Helsley, D S Lorrain, R A Rabin, Jerrold C Winter
Psychopharmacology October 1995 DOI: 10.1007/bf02246076 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | Rats (LSD-trained rats; rat brain tissue) |
| Interventions | p-chlorophenylalanine (PCPA) p-chloroamphetamine (PCA) |
| Topics | LSD Serotonin |
| Key findings | PCPA and PCA both depleted brain serotonin and 5-HIAA, but only PCPA caused supersensitivity to LSD's discriminative stimulus and a 46% increase in maximal 5-HT2C receptor-mediated phosphoinositide hydrolysis. The authors suggest this 5-HT2C upregulation mediates the supersensitivity to LSD's stimulus effects after serotonin depletion. |
Abstract
The present study was designed to determine the effects of p-chlorophenylalanine (PCPA) and p-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.
Comparable studies
Other preclinical and animal studies on LSD, most cited first.
Citations in the library
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- Hallucinogen-like actions of 5-methoxy-N,N-diisopropyltryptamine in mice and rats. Pharmacology, Biochemistry, and Behavior 2006
- d-Lysergic Acid Diethylamide (LSD) as a Model of Psychosis: Mechanism of Action and Pharmacology International Journal of Molecular Sciences November 23, 2016
- Lysergic acid diethylamide and [−]-2,5-dimethoxy-4-methylamphetamine increase extracellular glutamate in rat prefrontal cortex Brain Research August 27, 2004
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Cites 11
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- The role of the 5-HT2A and 5-HT2C receptors in the stimulus effects of hallucinogenic drugs. I: Antagonist correlation analysis. Psychopharmacology October 1995
and 6 more in the library