Neurotransmitter basis of the behavioral effects of hallucinogens.
Richard H. Rech, Randall L. Commissaris
Neuroscience & Biobehavioral Reviews 1982 DOI: 10.1016/0149-7634(82)90035-5 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal behavioral pharmacology study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | LSD DOM DMT mescaline 6-OHDA 5 7-DHT metergoline d-amphetamine phenobarbital |
| Topics | LSD Mescaline Serotonin |
| Keywords | Brain Animals Rats N,N-Dimethyltryptamine Metergoline Receptors, serotonin Hallucinogens Behavior, animal Conditioning, operant Reinforcement schedule Dose-response relationship, drug Dom 2,5-dimethoxy-4-methylamphetamine |
| Key points | Indole and phenethylamine hallucinogens disrupted fixed-ratio operant performance by producing pauses whose potency correlated with human hallucinogenic potency. Serotonin depletion potentiated these effects, and metergoline shifted dose-response curves rightward, indicating an agonistic action at central serotonin receptors. The authors propose the two drug classes may interact with brain serotonin systems by somewhat different mechanisms. |
Abstract
Indole and phenethylamine-type hallucinogenic drugs were studied in an FR-40 operant behavioral procedure programmed to quantify "pausing,"-a behavioral disruption somewhat specific to hallucinatory drug effects. LSD, DOM, DMT and mescaline showed a potency ratio to produce pausing that is well correlated with the hallucinatory potencies of these agents in man. Furthermore, combinations of the hallucinogens interact with potentiation to cause FR-40 pausing, whereas a variety of non-hallucinogenic psychoactive drugs failed to shift the dose-response patterns of pausing for DOM or LSD. Depletion of brain catecholamines by pretreatment with intraventricular 6-OHDA reduced baseline FR-40 rates and attenuated the disruptive effects of d-amphetamine, but failed to modify the dose-response patterns of indole and phenethylamine hallucinogens. On the other hand, pretreatment with intraventricular 5,7-DHT to deplete brain 5-HT potentiated the pause-producing effects of the hallucinogens, although the disruptive effects of phenobarbital were not altered by this pretreatment. Injection of 5,7-DHT into the medial forebrain bundle at the hypothalamic level slightly potentiated LSD, attenuated DOM, and did not affect the pausing produced by mescaline. Metergoline pretreatment shifted the LSD and DMT dose-response curves for pausing to the right by a factor of 2--3, but shifted the DOM and mescaline dose-response patterns to a much greater extent. Metergoline alone slightly increased FR-40 response rates and decreased pausing from baseline levels. The patterns of imparied FR-40 performance induced by d-amphetamine and phenobarbital were unaltered by pretreatment with metergoline. The indole and phenethylamine classes of hallucinogens appear to disrupt this behavior by an agonistic effect at central 5-HT receptors. However, the two classes of drugs may interact with brain 5-HT systems by somewhat different mechanisms.
Comparable studies
Other preclinical and animal studies on mescaline, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. C57BL/6J mice | 2020 | Experimental study with dose-response experiments | |
| Brain mechanisms of hallucinogens and entactogens Humans and rats | 2001 | Review | |
| Effects of hallucinogenic agents mescaline and phencyclidine on zebrafish behavior and physiology Zebrafish (Danio rerio) | 2012 | Experimental study | |
| Lysergic Acid Diethylamide- and Mescaline-Induced Attenuation of the Effect of Punishment in the Rat Rats | 1976 | Experimental study | |
| Dihydrobenzofuran Analogues of Hallucinogens. 3. Models of 4-Substituted (2,5-Dimethoxyphenyl)alkylamine Derivatives with Rigidified Methoxy Groups Rats (trained to discriminate saline from LSD tartrate) and rat cortical and... | 1996 | In vivo drug discrimination assay and in vitro radioligand binding assay |
Citations in the library
Cited by 6
- Animal Models of Serotonergic Psychedelics ACS Chemical Neuroscience September 24, 2012
- Opposite effects of N,N-dimethyltryptamine (DMT) and 5-methoxy-n,n-dimethyltryptamine (5-MeODMT) on acoustic startle: spinal vs brain sites of action. Neuroscience & Biobehavioral Reviews 1982
- Behavioral effects of intracerebroventricular administration of LSD, DOM, mescaline or lisuride Pharmacology, Biochemistry, and Behavior August 1, 1984
- Variability in the effects of 4-bromo-2,5-dimethoxyamphetamine (DOB) on operant behavior of squirrel monkeys. Pharmacology, Biochemistry, and Behavior February 1988
- Studies on the specificity of neurochemical and behavioral effects of LSD-25. Pharmacology, Biochemistry, and Behavior February 1986
and 1 more in the library
Cites 5
- Antagonism of the behavioral effects of 2,5-dimethoxy-4-methylamphetamine (DOM) and quipazine by metergoline. Pharmacology, Biochemistry, and Behavior October 1981
- The behavioral effects of hallucinogens in rats following 5,7-dihydroxytryptamine administration into the medial forebrain bundle. Pharmacology, Biochemistry, and Behavior June 1981
- Central 5-hydroxytryptamine and the effects of hallucinogens and phenobarbital on operant responding in rats. Pharmacology, Biochemistry, and Behavior May 1981
- The effects of d-lysergic acid diethylamide (LSD), 2,5-dimethoxy-4-methylamphetamine (DOM) and d-amphetamine on operant responding in control and 6-hydroxydopamine-treated rats. Pharmacology, Biochemistry, and Behavior November 1980
- Enhancement of the behavioral effects of 2,5-dimethoxy-4-methyl-amphetamine (DOM) by pretreatment with p-chlorophenylalanine. Pharmacology, Biochemistry, and Behavior October 1980