title: Dorsal-striatal 5-HT₂A and 5-HT₂C receptors control impulsivity and perseverative responding in the 5-choice serial reaction time task.
abstract: BACKGROUND
  Prefrontal cortex (PFC) and dorsal striatum are part of the neural circuit critical for executive attention. The relationship between 5-HT and aspects of attention and executive control is complex depending on experimental conditions and the level of activation of different 5-HT receptors within the nuclei of corticostriatal circuitry.
  
  
  OBJECTIVE
  The present study investigated which 5-HT(2A) and 5-HT(2C) receptors in the dorsomedial-striatum (dm-STR) contribute to executive attention deficit induced by blockade of NMDA receptors in the PFC.
  
  
  RESULTS
  Executive attention was assessed by the five-choice serial reaction time task (5-CSRTT), which provides indices of attention (accuracy) and those of executive control over performance such as premature (an index of impulsivity) and perseverative responding. The effects of targeted infusion in dm-STR of 100 and 300 ng/μl doses of the selective 5-HT(2A) antagonist M100907 and 1 and 3 μg/μl doses of 5-HT(2C) agonist Ro60-0175 was examined in animals injected with 50 ng/μl dose of a competitive NMDA receptor antagonist 3-(R)-2-carboxypiperazin-4-phosphonic acid (CPP) in the mPFC. Blockade of NMDA receptors impaired accuracy as well as executive control as shown by increased premature and perseverative responding. The CPP-induced premature and perseverative over-responding were dose-dependently prevented by both M100907 and Ro60-0175. Both drugs partially removed the CPP-induced accuracy deficit but only at the highest dose tested.
  
  
  CONCLUSIONS
  It is suggested that in the dorsal striatum, 5-HT by an action on 5-HT(2A) and 5-HT(2C) receptors may integrate the glutamate corticostriatal inputs critical for different aspects of the 5-CSRT task performance.
authors: Department of Neuroscience, Istituto di Ricerche Farmacologiche "Mario Negri", via G. La Masa 19, Milan 20156, Italy.
authors: Laura
authors: L
authors: Agnoli
authors: Mirjana
authors: M
authors: Carli
mesh_terms: D000818:Animals; D021461:Animals, Outbred Strains; D001288:Attention / Q000187:drug effects / Q000502:physiology; D002755:Choice Behavior / Q000187:drug effects / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005021:Ethylamines / Q000008:administration & dosage / Q000494:pharmacology; D005464:Fluorobenzenes / Q000008:administration & dosage / Q000494:pharmacology; D007175:Impulsive Behavior / Q000503:physiopathology*; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D010879:Piperazines / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D044402:Receptor, Serotonin, 5-HT2A / Q000502:physiology*; D044405:Receptor, Serotonin, 5-HT2C / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology; D012691:Serial Learning / Q000187:drug effects / Q000502:physiology; D058826:Serotonin 5-HT2 Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D005021:Ethylamines; D005464:Fluorobenzenes; D007211:Indoles; D010879:Piperazines; 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; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; C079049:volinanserin