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Behavioral sensitivity to LSD: Dependency upon the pattern of central 5HT depletion

James A. Joseph, James B. Appel

Pharmacology, Biochemistry, and Behavior May 1, 1977 DOI: 10.1016/0091-3057(77)90108-3 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Experimental study Peer reviewed
Population Rats
Interventions p-chloroamphetamine 5 7-dihydroxytryptamine p-chlorophenylalanine LSD
Dose 0.02 mg/kg
Duration 12 days after 5,7-DHT administration
Topics Serotonin LSD
Keywords 5,7-dihydroxytryptamine 5-HT Receptor P-chloroamphetamine Sensitivity control systems Endocrinology Pharmacology
Citations 18
Key findings Only 5,7-dihydroxytryptamine, not p-chloroamphetamine, increased sensitivity to a low dose of LSD, disrupting bar-press behavior, suggesting a specific pattern of serotonin depletion is required.

Abstract

Two experiments were carried out using a fixed ratio (FR) schedule of water reinforcement to determine the efficacy of two serotonin (5HT) depleting agents (p-chloroamphetamine, 5, 7-dihydroxytryptamine) in altering sensitivity to a low dose of LSD (0.02 MG/KG). The results showed that while both p-chloroamphetamine (PCA) and 5, 7 dihydroxytryptamine (5, 7 DHT) were efficacious in reducing whole brain 5HT, only 5, 7 DHT altered LSD sensitivity such that a 0.02 mg/kg dose of LSD given 12 days after 5, 7 DHT administration disrupted bar press behavior. This was not observed in animals given PCA within similar parameters. Moreover, 4 animals given PCA that did not show increased sensitivity to LSD, did show behavioral disruption to LSD (0.02 mg/kg when they were pretreated with p-chlorophenylalanine, Results are discussed on terms of a possible particular pattern of 5HT depletion that must be achieved before sensitivity to LSD is observed.

Comparable studies

Other preclinical and animal studies on LSD, most cited first.

Study Year Design Participants
Transcriptome Fingerprints Distinguish Hallucinogenic and Nonhallucinogenic 5-Hydroxytryptamine 2A Receptor Agonist Effects in Mouse Somatosensory Cortex Human embryonic kidney 293 cells stably expressing 5-HT2ARs; wild-type and 5-HT2AR... 2003 Experimental study
Evidence for a central 5‐hydroxytryptamine receptor stimulation by lysergic acid diethylamide Rats 1968 Experimental study
Psychedelics, but Not Ketamine, Produce Persistent Antidepressant-like Effects in a Rodent Experimental System for the Study of Depression Rats 2020 Preclinical study
Lysergic acid diethylamide (LSD) promotes social behavior through mTORC1 in the excitatory neurotransmission Male mice 2021 Multidisciplinary experimental study with in vivo electrophysiology, optogenetics, behavioral paradigms, molecular biology, and conditional knockout mice
A non-hallucinogenic LSD analog with therapeutic potential for mood disorders. Mice and cultured rat cortical neurons 2023 Preclinical study

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