Neuropharmacological reassessment of the discriminative stimulus properties ofd-lysergic acid diethylamide (LSD)
Kathryn A. Cunningham, J. B. Appel
Psychopharmacology 1987 DOI: 10.1007/bf00690929 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Drug discrimination study Peer reviewed |
|---|---|
| Sample size | 23 |
| Population | Male Sprague-Dawley rats |
| Interventions | LSD 8-OHDPAT Ru 24969 MCPP TFMPP quipazine BC 105 BOL Ly 53857 metergoline ketanserin pipenperone spiperone |
| Dose | 0.08 mg/kg |
| Topics | LSD Serotonin |
| Keywords | Quipazine Metergoline Ketanserin Spiperone 5-ht1 receptor Pharmacology 8-oh-dpat 5-HT Receptor Cyproheptadine Hallucinogen 5-ht2 receptor Endocrinology |
| Citations | 84 |
| Key points | 5-HT2 antagonists block the discriminative stimulus effects of LSD, while 5-HT1 agonists do not mimic LSD, indicating 5-HT2 receptors are primarily responsible for LSD's behavioral effects. |
Abstract
The neuropharmacological mechanisms underlying the behavioral effects of d-lysergic acid diethylamide (LSD) were assessed by comparing the discriminative stimulus properties of LSD with those of agonists and antagonists that act selectively at putative serotonin (5-hydroxytryptamine; 5-HT) receptor subtypes (5-HT1 and 5-HT2). Male Sprague-Dawley rats (N = 23) were trained to discriminate LSD (0.08 mg/kg) from saline and given substitution tests with the following agents: 8-hydroxy-2(di-n-propyl-amino) tetralin (8-OHDPAT; 0.02-0.64 mg/kg), Ru 24969 (0.2-3.2 mg/kg), m-chlorophenylpiperazine (MCPP; 0.1-1.6 mg/kg), 1-(m-trifluoromethylphenyl)piperazine (TFMPP; 0.1-1.6 mg/kg), and quipazine (0.2-3.2 mg/kg). Only quipazine mimicked LSD. In combination tests, BC 105 (0.2-3.2 mg/kg), 2-bromolysergic acid diethylamide (BOL; 0.1-1.6 mg/kg), Ly 53857 (0.4-3.2 mg/kg), metergoline (0.05-0.8 mg/kg), ketanserin (0.2-3.2 mg/kg), and pipenperone (0.0025-0.08 mg/kg), all of which act as 5-HT2 antagonists, blocked the LSD cue; only spiperone (0.02-0.32 mg/kg) was without effect. Although commonalities may exist among "5-HT agonists", the present results demonstrate that such "agonists" are not identical. Since putative 5-HT1 agonists do not mimic LSD and the LSD cue is potently blocked by 5-HT2 antagonists, it appears that 5-HT2 neuronal systems are of greater importance than 5-HT1 systems in mediating the discriminative stimulus and, perhaps, other effects of LSD.
Comparable studies
Other preclinical and animal studies on LSD, most cited first.
Citations in the library
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- The hallucinogenic world of tryptamines: an updated review. Archives of Toxicology August 1, 2015
- The promises and perils of psychedelic pharmacology for psychiatry. Nature Reviews Drug Discovery June 1, 2022
- Hallucinogen-like actions of 5-methoxy-N,N-diisopropyltryptamine in mice and rats. Pharmacology, Biochemistry, and Behavior 2006
- Dihydrobenzofuran Analogues of Hallucinogens. 3. Models of 4-Substituted (2,5-Dimethoxyphenyl)alkylamine Derivatives with Rigidified Methoxy Groups Journal of Medicinal Chemistry 1996
and 41 more in the library
Cites 3
- Citalopram antagonizes the stimulation by lysergic acid diethylamide of presynaptic inhibitory serotonin autoreceptors in the rat hypothalamus. Journal of Pharmacology and Experimental Therapeutics July 1, 1982
- Antagonism of the effects of the hallucinogen DOM and the purported 5-HT agonist quipazine by 5-HT2 antagonists. European Journal of Pharmacology July 1, 1983
- 8-hydroxy-2-(di-n-propylamino)tetralin, 8-OH-DPAT, a potent and selective simplified ergot congener with central 5-HT-receptor stimulating activity Journal of Neural Transmission September 1, 1982