Journal article
The role of serotonin-2 (5-HT2) and dopamine receptors in the behavioral actions of the 5-HT2A/2C agonist, DOI, and putative 5-HT2C inverse agonist, SR46349B
PSYCHOPHARMACOLOGY, v 213(2-3), pp 393-401
01 Feb 2011
PMID: 20652541
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Atypical antipsychotic efficacy is often attributed to actions at serotonin-2 (5-HT2) and dopamine receptors, indicating a potential benefit of understanding the interplay between these systems. Currently, it is known that 5-HT2 receptors modulate dopamine release, although the role of specific dopamine receptors in 5-HT2-mediated behavior is not well understood.
We examined the role of 5-HT2A, 5-HT2C, and dopamine (D1 and D2) receptors in the behavioral response to a 5-HT2A/2C agonist (DOI) and 5-HT2A/2C antagonist (SR46349B).
Effects were assessed by measuring rabbit head bobs (previously characterized as 5-HT2A receptor-mediated) and body shakes (5-HT2C-mediated).
As expected, DOI produced head bobs and body shakes, and these DOI-elicited behaviors were attenuated by the SR46349B pretreatment. Unexpectedly, SR46349B also induced head bobs when administered alone. However, SR46349B-elicited head bobs are distinguishable from those produced by DOI since the 5-HT2A antagonist, ketanserin, only attenuated DOI-elicited head bobs. Conversely, 5-HT2C ligands (SB242084 and SB206553) inhibited SR46349B but not DOI-induced head bobs. Furthermore, when administered alone, SB206553 (a 5-HT2C inverse agonist) produced head bobs, indicating the behavior can be either 5-HT2A or 5-HT2C mediated. Next, it was revealed that D1 and D2 receptors play a role in DOI-elicited head bobs, but only D1 receptors are required for SR46349B-elicited head bobs.
5-HT2A receptor agonism and 5-HT2C inverse agonism produce the same behavior, likely due to similar downstream actions at D1 receptors. Consequently, 5-HT2C agonism or D1 agonism may be effective therapies for disorders, such as schizophrenia, currently being treated with 5-HT2A antagonists.
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Details
- Title
- The role of serotonin-2 (5-HT2) and dopamine receptors in the behavioral actions of the 5-HT2A/2C agonist, DOI, and putative 5-HT2C inverse agonist, SR46349B
- Creators
- Laura C. Scarlota - Drexel UniversityJohn A. Harvey - Drexel UniversityVincent J. Aloyo - Drexel University
- Publication Details
- PSYCHOPHARMACOLOGY, v 213(2-3), pp 393-401
- Publisher
- Springer Nature
- Number of pages
- 9
- Grant note
- R37MH016841 / 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) United States Public Health Service from the 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:000286938000014
- Scopus ID
- 2-s2.0-79952489193
- Other Identifier
- 991019167663904721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Neurosciences
- Pharmacology & Pharmacy
- Psychiatry