title: 5-HT(2A) and 5-HT(2C) receptors exert opposing effects on locomotor activity in mice.
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 (> 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.
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093-0804, USA.
authors.forename: Adam L
authors.initials: AL
authors.lastname: Halberstadt
authors.forename: Iris
authors.initials: I
authors.lastname: van der Heijden
authors.forename: Michael A
authors.initials: MA
authors.lastname: Ruderman
authors.forename: Victoria B
authors.initials: VB
authors.lastname: Risbrough
authors.forename: Jay A
authors.initials: JA
authors.lastname: Gingrich
authors.forename: Mark A
authors.initials: MA
authors.lastname: Geyer
authors.forename: Susan B
authors.initials: SB
authors.lastname: Powell