Impulsive action induced by amphetamine, cocaine and MK801 is reduced by 5-HT(2C) receptor stimulation and 5-HT(2A) receptor blockade

Neuropharmacology. 2011 Sep;61(3):468-77. doi: 10.1016/j.neuropharm.2011.02.025. Epub 2011 Mar 21.


Previous work has shown that 5-HT(2C) receptor agonists and 5-HT(2A) receptor antagonists reduce impulsive action, as well as the locomotor stimulant effect of psychomotor stimulants. Since psychomotor stimulants also increase impulsive action we examined the effects of the 5-HT(2C) receptor agonist Ro60-0175, and the 5-HT(2A) receptor antagonist M100907 on impulsive action induced by amphetamine, cocaine and the NMDA receptor antagonist MK801 (dizocilpine). Impulsive action was measured in adult male Long-Evans rats as premature responding in the 5-choice serial reaction time (5-CSRT) test. Initially, we determined that amphetamine (0.3 mg/kg), cocaine (15 mg/kg) and MK801 (0.03 mg/kg) induced comparable premature response rates of approximately 50-70 per session, compared to 10-15 responses under baseline conditions. Each drug and its vehicle were then tested in combination with Ro60-0175 (0.1 and 0.6 mg/kg) or its vehicle, or M100907 (0.5 mg/kg) or its vehicle. At 0.1 mg/kg Ro60-0175 did not modify the effects of amphetamine, cocaine or MK801. In contrast, the 0.6 mg/kg dose reduced premature responses induced by amphetamine, cocaine and MK801. M100907 also reduced premature responding induced by all three of these drugs. In general, treatment with Ro60-0175 or M100907 by itself did not consistently alter any of the other aspects of task performance in the 5-CSRT test including number of trials completed, and accuracy of responding. These data show that activation of 5-HT(2C) receptors and blockade of 5-HT(2A) receptors have seemingly similar functional effects on a measure of impulsive action.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphetamine / administration & dosage
  • Amphetamine / toxicity
  • Animals
  • Behavior, Animal / drug effects
  • Central Nervous System Stimulants / administration & dosage
  • Central Nervous System Stimulants / toxicity*
  • Cocaine / administration & dosage
  • Cocaine / toxicity
  • Dizocilpine Maleate / administration & dosage
  • Dizocilpine Maleate / toxicity
  • Dose-Response Relationship, Drug
  • Ethylamines / therapeutic use
  • Excitatory Amino Acid Antagonists / administration & dosage
  • Excitatory Amino Acid Antagonists / toxicity*
  • Fluorobenzenes / therapeutic use
  • Impulsive Behavior / chemically induced
  • Impulsive Behavior / drug therapy*
  • Indoles / therapeutic use
  • Male
  • Piperidines / therapeutic use
  • Psychomotor Performance / drug effects
  • Rats
  • Rats, Long-Evans
  • Receptor, Serotonin, 5-HT2A / chemistry*
  • Receptor, Serotonin, 5-HT2C / chemistry*
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Serotonin 5-HT2 Receptor Agonists / therapeutic use*
  • Serotonin 5-HT2 Receptor Antagonists / therapeutic use*


  • Central Nervous System Stimulants
  • Ethylamines
  • Excitatory Amino Acid Antagonists
  • Fluorobenzenes
  • Indoles
  • Piperidines
  • Receptor, Serotonin, 5-HT2A
  • Receptor, Serotonin, 5-HT2C
  • Receptors, N-Methyl-D-Aspartate
  • Ro 60-0175
  • Serotonin 5-HT2 Receptor Agonists
  • Serotonin 5-HT2 Receptor Antagonists
  • Dizocilpine Maleate
  • Amphetamine
  • volinanserin
  • Cocaine