5-HT2A and 5-HT2C Receptors Exert Opposing Effects on Locomotor Activity in Mice

Mar 27, 2009Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Two serotonin receptors have opposite effects on movement in mice

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Abstract

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 mice lacking 5-HT(2A) receptors, indicating their involvement.
  • The reduction in locomotor activity caused by 10 mg/kg DOI was enhanced in 5-HT(2A) receptor knockout mice.
  • Pretreatment with a selective 5-HT(2C/2B) antagonist reduced the decrease in locomotor activity from 10 mg/kg DOI, suggesting mediation by 5-HT(2C) receptors.
  • A selective 5-HT(2C) agonist produced decreased locomotor activity that was amplified in 5-HT(2A) knockout mice.
  • These findings indicate that both 5-HT(2A) and 5-HT(2C) receptors contribute to the effects of DOI on locomotor activity, potentially exerting opposing influences.

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