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.