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Journal article
Serotonergic and dopaminergic distinctions in the behavioral pharmacology of (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD)
Pharmacology, biochemistry and behavior, v 101(1), pp 69-76
01 Mar 2012
PMID: 22197710
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Abstract
Rationale: After decades of social stigma, hallucinogens have reappeared in the clinical literature demonstrating unique benefits in medicine. The precise behavioral pharmacology of these compounds remains unclear, however.
Objectives: Two commonly studied hallucinogens, (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD), were investigated both in vivo and in vitro to determine the pharmacology of their behavioral effects in an animal model.
Method: Rabbits were administered DOI or LSD and observed for head bob behavior after chronic drug treatment or after pretreatment with antagonist ligands. The receptor binding characteristics of DOI and LSD were studied in vitro in frontocortical homogenates from naive rabbits or ex vivo in animals receiving an acute drug injection.
Results: Both DOI- and LSD-elicited head bobs required serotonin(2A) (5-HT2A) and dopamine(1) (D-1) receptor activation. Serotonin(2B/2C) receptors were not implicated in these behaviors. In vitro studies demonstrated that LSD and the 5-HT2A/2C receptor antagonist, ritanserin, bound frontocortical 5-HT2A receptors in a pseudo-irreversible manner. In contrast, DOI and the 5-HT2A/2C receptor antagonist, ketanserin. bound reversibly. These binding properties were reflected in ex vivo binding studies. The two hallucinogens also differed in that LSD showed modest D-1 receptor binding affinity whereas DOI had negligible binding affinity at this receptor.
Conclusion: Although DOI and LSD differed in their receptor binding properties, activation of 5-HT2A and D-1 receptors was a common mechanism for eliciting head bob behavior. These findings implicate these two receptors in the mechanism of action of hallucinogens. (C) 2011 Elsevier Inc. All rights reserved.
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Details
- Title
- Serotonergic and dopaminergic distinctions in the behavioral pharmacology of (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD)
- Creators
- Emmanuelle A. D. Schindler - Drexel UniversityKuldip D. Dave - Drexel UniversityElaine M. Smolock - Drexel UniversityVincent J. Aloyo - Drexel UniversityJohn A. Harvey - Drexel University
- Publication Details
- Pharmacology, biochemistry and behavior, v 101(1), pp 69-76
- Publisher
- Elsevier
- Number of pages
- 8
- Grant note
- MH16841-40 / NIMH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH) R01MH016841 / NATIONAL INSTITUTE OF MENTAL HEALTH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000301017500010
- Scopus ID
- 2-s2.0-84855763519
- Other Identifier
- 991019167665104721
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Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Behavioral Sciences
- Neurosciences
- Pharmacology & Pharmacy