title: Impulsive action induced by amphetamine, cocaine and MK801 is reduced by 5-HT(2C) receptor stimulation and 5-HT(2A) receptor blockade.
abstract: 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.
authors.affiliation: Section of Biopsychology, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, Canada M5T 1R8. Paul_Fletcher@camh.net
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Fletcher
authors.forename: Zoë
authors.initials: Z
authors.lastname: Rizos
authors.forename: Kevin
authors.initials: K
authors.lastname: Noble
authors.forename: Guy A
authors.initials: GA
authors.lastname: Higgins
mesh_terms: D000661:Amphetamine / Q000008:administration & dosage / Q000633:toxicity; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000633:toxicity*; D003042:Cocaine / Q000008:administration & dosage / Q000633:toxicity; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005021:Ethylamines / Q000627:therapeutic use; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000633:toxicity*; D005464:Fluorobenzenes / Q000627:therapeutic use; D007175:Impulsive Behavior / Q000139:chemically induced / Q000188:drug therapy*; D007211:Indoles / Q000627:therapeutic use; D008297:Male; D010880:Piperidines / Q000627:therapeutic use; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D020318:Rats, Long-Evans; D044402:Receptor, Serotonin, 5-HT2A / Q000737:chemistry*; D044405:Receptor, Serotonin, 5-HT2C / Q000737:chemistry*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D058826:Serotonin 5-HT2 Receptor Agonists / Q000627:therapeutic use*; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000627:therapeutic use*
chemical_list: D000697:Central Nervous System Stimulants; D005021:Ethylamines; D018691:Excitatory Amino Acid Antagonists; D005464:Fluorobenzenes; D007211:Indoles; D010880:Piperidines; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D016194:Receptors, N-Methyl-D-Aspartate; C103848:Ro 60-0175; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D016291:Dizocilpine Maleate; D000661:Amphetamine; C079049:volinanserin; D003042:Cocaine