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Neuropharmacological reassessment of the discriminative stimulus properties of d-lysergic acid diethylamide (LSD).
Psychopharmacology (Berl). 1987; 91(1):67-73.P

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.

Authors

Cunningham KA
No affiliation info available
Appel JB
No affiliation info available

MeSH

AnimalsBrainDiscrimination LearningDose-Response Relationship, DrugLysergic Acid DiethylamideMaleRatsRats, Inbred StrainsReceptors, SerotoninSerotoninSerotonin Antagonists

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

3103161

Citation

Cunningham, K A., and J B. Appel. "Neuropharmacological Reassessment of the Discriminative Stimulus Properties of D-lysergic Acid Diethylamide (LSD)." Psychopharmacology, vol. 91, no. 1, 1987, pp. 67-73.
Cunningham KA, Appel JB. Neuropharmacological reassessment of the discriminative stimulus properties of d-lysergic acid diethylamide (LSD). Psychopharmacology (Berl). 1987;91(1):67-73.
Cunningham, K. A., & Appel, J. B. (1987). Neuropharmacological reassessment of the discriminative stimulus properties of d-lysergic acid diethylamide (LSD). Psychopharmacology, 91(1), 67-73.
Cunningham KA, Appel JB. Neuropharmacological Reassessment of the Discriminative Stimulus Properties of D-lysergic Acid Diethylamide (LSD). Psychopharmacology (Berl). 1987;91(1):67-73. PubMed PMID: 3103161.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neuropharmacological reassessment of the discriminative stimulus properties of d-lysergic acid diethylamide (LSD). AU - Cunningham,K A, AU - Appel,J B, PY - 1987/1/1/pubmed PY - 1987/1/1/medline PY - 1987/1/1/entrez SP - 67 EP - 73 JF - Psychopharmacology JO - Psychopharmacology (Berl) VL - 91 IS - 1 N2 - 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. SN - 0033-3158 UR - https://www.unboundmedicine.com/medline/citation/3103161/Neuropharmacological_reassessment_of_the_discriminative_stimulus_properties_of_d_lysergic_acid_diethylamide__LSD__ DB - PRIME DP - Unbound Medicine ER -