Neuropharmacological reassessment of the discriminative stimulus properties ofd-lysergic acid diethylamide (LSD)
Kathryn A. Cunningham, J. B. Appel
Psychopharmacology January 1, 1987 DOI: 10.1007/bf00690929 (opens in new tab) via OpenAlex
Summary
AI-generated from the abstractThe behavioral effects of LSD are mediated primarily through 5-HT2 serotonin receptors rather than 5-HT1 receptors. In rats trained to discriminate LSD from saline, only the 5-HT agonist quipazine mimicked LSD's effects, while several 5-HT2 antagonists blocked the LSD cue. Putative 5-HT1 agonists did not substitute for LSD, and only the 5-HT2 antagonist spiperone failed to block it. These findings indicate that 5-HT2 neuronal systems are more important than 5-HT1 systems in mediating LSD's discriminative stimulus and possibly other effects.
Study at a glance
| 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 |
| Citations | 84 |
| Key finding | 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.