| First Author | Halberstadt AL | Year | 2009 |
| Journal | Neuropsychopharmacology | Volume | 34 |
| Issue | 8 | Pages | 1958-67 |
| PubMed ID | 19322172 | Mgi Jnum | J:311462 |
| Mgi Id | MGI:6766485 | Doi | 10.1038/npp.2009.29 |
| Citation | Halberstadt AL, et al. (2009) 5-HT(2A) and 5-HT(2C) receptors exert opposing effects on locomotor activity in mice. Neuropsychopharmacology 34(8):1958-67 |
| abstractText | 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 (> or =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. |
