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

• Published in: Neuropharmacology 2011-09, Vol.61 (3), p.468-477
• Main Authors: Fletcher, Paul J, Rizos, Zoë, Noble, Kevin, Higgins, Guy A
• Format: Article
• Language: English
• Subjects: 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
• ISSN: 1873-7064
• DOI: 10.1016/j.neuropharm.2011.02.025

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.