Neurophysiological effects of hallucinogens on serotonergic neuronal systems.
Neuroscience & Biobehavioral Reviews 1982 DOI: 10.1016/0149-7634(82)90033-1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Theoretical or philosophical paper Peer reviewed |
|---|---|
| Population | Rats |
| Topics | Serotonin |
| Key points | The authors argue that the disinhibition hypothesis of hallucinogen action is inadequate because LSD's behavioral and neuronal effects do not correlate in time, raphe neurons do not develop tolerance to LSD, mescaline does not directly inhibit 5-HT neurons, and the non-hallucinogen lisuride does. They propose that hallucinogens act postsynaptically to sensitize serotonergic and noradrenergic receptors, which may account for altered perceptual reactivity. |
Abstract
Low intravenous doses of the hallucinogen d-lysergic acid diethylamide (LSD) markedly suppress the discharge of serotonin (5-HT)-containing neurons in the dorsal raphe nucleus of the rat. Microiontophoretically applied LSD also inhibits the firing of 5-HT neurons, indicating that the inhibitory effect is mediated directing on 5-HT neurons. Forebrain neurons receiving a major serotonergic input are relatively insensitive to LSD. Other indole hallucinogens (i.e., psilocin, dimethyltryptamine, and 5-methoxydimethyltryptamine) also preferentially inhibit raphe firing as compared to postsynaptic forebrain neurons. These observations led to the hypothesis that hallucinogens produce their psychoactive effects by acting preferentially upon 5-HT autoreceptors in the dorsal raphe allowing postsynaptic neurons to escape from the tonic inhibitory action of 5-HT neurons. However, problems exist with the concept that hallucinogens produce their psychoactive effects by disinhibiting postsynaptic neurons. First, the time course of the behavioral and neuronal effects of LSD do not correlate. Second, 5-HT neurons do not become tolerant to the inhibitory actions of LSD. Third, the hallucinogen mescaline fails to directly inhibit 5-HT neurons. Finally, the nonhallucinogen lisuride markedly suppresses the discharges of 5-HT neurons. These observations suggest that postsynaptic actions of hallucinogens may be of prime importance in producing their psychedelic effects. Evidence is presented to suggest that the hallucinogens may act postsynaptically to sensitize both serotonergic and noradrenergic receptors. It is suggested that a mechanism of receptor sensitization, in distinction to disinhibition, might account for the altered perceptual reactivity produced by these drugs.
Comparable studies
Other preclinical and animal studies on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) | 1987 | Experimental study | |
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain | 1987 | Animal experiment | |
| Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells | 2006 | In vitro laboratory study |
Citations in the library
Cited by 9
- Concise Large-Scale Synthesis of Psilocin and Psilocybin, Principal Hallucinogenic Constituents of “Magic Mushroom” Journal of Natural Products May 30, 2003
- Mechanisms and molecular targets surrounding the potential therapeutic effects of psychedelics. Molecular Psychiatry September 1, 2023
- Occurrence and use of hallucinogenic mushrooms containing psilocybin alkaloids TemaNord May 19, 2009
- The Native American Church, Peyote, and Health: Expanding Consciousness for Healing Purposes Contemporary Justice Review December 1, 2007
- Ultrarunners and Chance Encounters with "Absolute Unitary Being" Anthropology of Consciousness September 1, 2004
and 4 more in the library
Cites 7
- Lysergic Acid Diethylamide: Sensitive Neuronal Units in the Midbrain Raphe Science August 16, 1968
- Evidence for a central 5‐hydroxytryptamine receptor stimulation by lysergic acid diethylamide British Journal of Pharmacology September 1, 1968
- An Animal Behavior Model for Studying the Actions of LSD and Related Hallucinogens Science November 12, 1976
- Effects of Hallucinogenic and Tranquilizing Drugs on Serotonin Evoked Uterine Contractions. Experimental Biology and Medicine 1956
- Dissociations Between the Effects of LSD on Behavior and Raphe Unit Activity in Freely Moving Cats Science August 3, 1979
and 2 more in the library