Effect of hallucinogens on spontaneous and sensory-evoked locus coeruleus unit activity in the rat: reversal by selective 5-HT2 antagonists.
K Rasmussen, George K. Aghajanian
Brain Research October 1, 1986 DOI: 10.1016/0006-8993(86)91090-5 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Anesthetized rats |
| Interventions | LSD mescaline DOM LY 53857 ritanserin (+)-amphetamine |
| Dose | LSD 5-10 micrograms/kg; mescaline 2 mg/kg; DOM 20-80 micrograms/kg; LY 53857 0.02-0.8 mg/kg; ritanserin 0.1-0.3 mg/kg; (+)-amphetamine 0.5 mg/kg |
| Topics | LSD Mescaline |
| Keywords | Locus coeruleus Animals Rats, inbred strains Dextroamphetamine Ergolines Piperidines Ritanserin Hallucinogens Evoked potentials, somatosensory Male Dom 2,5-dimethoxy-4-methylamphetamine |
| Key findings | LSD, mescaline, and DOM decreased spontaneous locus coeruleus activity while facilitating sensory-evoked activation, and both effects were completely reversed by the 5-HT2 antagonists LY 53857 and ritanserin. LY 53857 did not reverse amphetamine's effects on the same neurons. The authors suggest these shared hallucinogen actions are mediated by 5-HT2 receptors located outside the locus coeruleus. |
Abstract
As previously reported, systemic administration of the hallucinogens D-lysergic acid diethylamide (LSD) (5-10 micrograms/kg) and mescaline (2 mg/kg) in the anesthetized rat produced a decrease in spontaneous activity but, paradoxically, facilitated activation of locus coeruleus (LC) neurons by sciatic nerve stimulation. In the present study, the hallucinogen 2,5-dimethoxy-4-methylamphetamine (DOM) (20-80 micrograms/kg) was found to have similar effects. Systemic administration of the selective 5-HT2 antagonists LY 53857 (0.02-0.8 mg/kg) and ritanserin (0.1-0.3 mg/kg) completely reversed both actions of the hallucinogens on the LC. In contrast, LY 53857 did not reverse the effects of (+)-amphetamine (0.5 mg/kg) on the spontaneous or sensory-evoked activity of the LC. These results suggest that the common actions of indoleamine and phenethylamine hallucinogens displayed in the LC are mediated via 5-HT2 receptors; however, these receptors appear to be located outside the LC itself.
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 33
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- The neural basis of psychedelic action. Nature Neuroscience October 24, 2022
- Shared and Distinct Brain Regions Targeted for Immediate Early Gene Expression by Ketamine and Psilocybin ACS Chemical Neuroscience January 11, 2023
- d-Lysergic Acid Diethylamide (LSD) as a Model of Psychosis: Mechanism of Action and Pharmacology International Journal of Molecular Sciences November 23, 2016
- Psilocybin dose-dependently causes delayed, transient headaches in healthy volunteers. Drug and Alcohol Dependence June 1, 2012
and 28 more in the library
Cites 8
- Evidence for 5-HT2 involvement in the mechanism of action of hallucinogenic agents. Life Sciences December 17, 1984
- Lysergic Acid Diethylamide: Sensitive Neuronal Units in the Midbrain Raphe Science August 16, 1968
- Activity of serotonin-containing neurons in nucleus centralis superior of freely moving cats. Experimental Neurology February 1, 1984
- The effects of lysergic acid diethylamide and mescaline-derived hallucinogens on sensory-integrative function: tactile startle. Journal of Pharmacology and Experimental Therapeutics December 1, 1978
- The 5HT2 antagonist pirenperone reverses disruption of FR-40 by hallucinogenic drugs. Pharmacology, Biochemistry, and Behavior May 1985
and 3 more in the library