5-HT_2A and 5-HT_2C Receptors Exert Opposing Effects on Locomotor Activity in Mice
Adam L. Halberstadt, Iris Van der Heijden, Michael A Ruderman, Victoria B Risbrough, Jay A Gingrich, Mark A. Geyer, Susan B Powell
Neuropsychopharmacology July 1, 2009 DOI: 10.1038/npp.2009.29 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice (including 5-HT2A receptor knockout mice) |
| Interventions | DOI SER-082 WAY 161 503 |
| Dose | DOI 0.625–5.0 mg/kg, 10 mg/kg; SER-082 and WAY 161,503 doses not stated |
| Topics | Serotonin |
| Keywords | Hallucinogen Mice Locomotor activity Knockout Doi |
| Key findings | DOI's effects on locomotor activity in mice involve opposing contributions from 5-HT2A (increasing activity) and 5-HT2C (decreasing activity) receptors. |
Abstract
Although it is well established that hallucinogens act as 5-HT_2A and 5-HT_2C receptor agonists, little is known about the relative contributions of 5-HT_2A and 5-HT_2C receptors to the acute behavioral effects of these drugs. The behavioral pattern monitor was used to characterize the effects of the hallucinogen 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) on locomotor and investigatory behavior in mice. Studies were also conducted to assess the contributions of 5-HT_2A and 5-HT_2C receptors to the behavioral effects of DOI. DOI produced an inverted U-shaped dose–response function, with lower doses (0.625–5.0 mg/kg) increasing and higher doses (⩾10 mg/kg) decreasing locomotor activity. The increase in locomotor activity induced by 1.0 mg/kg DOI was absent in 5-HT_2A receptor KO mice, suggesting the involvement of 5-HT_2A receptors. The reduction in locomotor activity produced by 10 mg/kg DOI was potentiated in 5-HT_2A KO mice and attenuated by pretreatment with the selective 5-HT_2C/2B antagonist SER-082. These data indicate that the decrease in locomotor activity induced by 10 mg/kg DOI is mediated by 5-HT_2C receptors, an interpretation that is supported by the finding that the selective 5-HT_2C agonist WAY 161,503 produces reductions in the locomotor activity that are potentiated in 5HT_2A KO mice. These results show for the first time that 5-HT_2A and 5-HT_2C receptors both contribute to the effects of DOI on locomotor activity in mice. Furthermore, these data also suggest that 5-HT_2A and 5-HT_2C receptors exert opposing effects on locomotor activity.
Comparable studies
Other preclinical and animal studies on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) | 1987 | Experimental study | |
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain | 1987 | Animal experiment | |
| Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells | 2006 | In vitro laboratory study |
Citations in the library
Cited by 69
- Differential contributions of serotonin receptors to the behavioral effects of indoleamine hallucinogens in mice Journal of Psychopharmacology December 8, 2010
- Animal Models of Serotonergic Psychedelics ACS Chemical Neuroscience September 24, 2012
- Effects of hallucinogenic agents mescaline and phencyclidine on zebrafish behavior and physiology Progress in Neuro-Psychopharmacology and Biological Psychiatry January 10, 2012
- Maternal Influenza Viral Infection Causes Schizophrenia-Like Alterations of 5-HT 2A and mGlu 2 Receptors in the Adult Offspring Journal of Neuroscience February 2, 2011
- The serotonin 2C receptor potently modulates the head-twitch response in mice induced by a phenethylamine hallucinogen Psychopharmacology February 19, 2010
and 64 more in the library
Cites 20
- Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Neuroreport December 1, 1998
- Serotonin research: contributions to understanding psychoses TIPS - Trends in Pharmacological Sciences August 1, 2008
- Transcriptome Fingerprints Distinguish Hallucinogenic and Nonhallucinogenic 5-Hydroxytryptamine 2A Receptor Agonist Effects in Mouse Somatosensory Cortex Journal of Neuroscience October 1, 2003
- Do functional relationships exist between 5-HT1A and 5-HT2 receptors? Pharmacology, Biochemistry, and Behavior August 1, 1990
- 5-HT2 receptors exert a state-dependent regulation of dopaminergic function: studies with MDL 100,907 and the amphetamine analogue, 3,4-methylenedioxymethamphetamine European Journal of Pharmacology November 1, 1992
and 15 more in the library