Neuropharmacological reassessment of the discriminative stimulus properties of d-lysergic acid diethylamide (LSD)

• Published in: Psychopharmacologia Vol. 91; no. 1; pp. 67 - 73
• Main Authors: CUNNINGHAM, K. A, APPEL, J. B
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01-01-1987
• Subjects: Animals; Applied sciences; Brain - drug effects; Discrimination Learning; Dose-Response Relationship, Drug; Exact sciences and technology; Lysergic Acid Diethylamide - pharmacology; Male; Other techniques and industries; Rats; Rats, Inbred Strains; Receptors, Serotonin - drug effects; Serotonin - pharmacology; Serotonin Antagonists - pharmacology
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/BF00690929

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.