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Investigating glutamatergic mechanism in attention and impulse control using rats in a modified 5-choice serial reaction time task.

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  • المؤلفون: Benn A;Benn A; Robinson ES; Robinson ES
  • المصدر:
    PloS one [PLoS One] 2014 Dec 19; Vol. 9 (12), pp. e115374. Date of Electronic Publication: 2014 Dec 19 (Print Publication: 2014).
  • نوع النشر :
    Journal Article; Research Support, Non-U.S. Gov't
  • اللغة:
    English
  • معلومة اضافية
    • المصدر:
      Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
    • بيانات النشر:
      Original Publication: San Francisco, CA : Public Library of Science
    • الموضوع:
    • نبذة مختصرة :
      The 5-choice serial reaction time task (5CSRTT) has been widely used to study attention and impulse control in rodents. In order to mimic cognitive impairments in psychiatry, one approach has been to use acute administration of NMDA antagonists. This disruption in glutamatergic transmission leads to impairments in accuracy, omissions, and premature responses although findings have been inconsistent. In this study, we further investigated glutamatergic mechanisms using a novel version of the 5CSRTT, which we have previously shown to be more sensitive to cognitive enhancers. We first investigated the effects of systemic treatment with NMDA antagonists. We also carried out a preliminary investigation using targeted medial prefrontal cortex infusions of a NMDA antagonist (MK801), mGluR2/3 antagonist (LY341495), and mGluR7 negative allosteric modulator (MMPIP). Acute systemic administration of the different NMDA antagonists had no specific effects on accuracy. At higher doses PCP, ketamine, and memantine, increased omissions and affected other measures suggesting a general disruption in task performance. Only MK801 increased premature responses, and reduced omissions at lower doses suggesting stimulant like effects. None of the NMDA antagonists affected accuracy or any other measures when tested using a short stimulus challenge. Infusions of MK801 had no effect on accuracy but increased premature responses following infralimbic, but not prelimbic infusion. LY341495 had no effects in either brain region but a decrease in accuracy was observed following prelimbic infusion of MMPIP. Contrary to our hypothesis, disruptions to glutamate transmission using NMDA antagonists did not induce any clear deficits in accuracy in this modified version of the 5CSRTT. We also found that the profile of effects for MK801 differed from those observed with PCP, ketamine, and memantine. The effects of MK801 in the infralimbic cortex add to the literature indicating this brain region and glutamate play an important role in impulse control.
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    • Grant Information:
      United Kingdom WT_ Wellcome Trust; G0700980 United Kingdom MRC_ Medical Research Council; 084621/Z/08/Z United Kingdom WT_ Wellcome Trust
    • الرقم المعرف:
      0 (Amino Acids)
      0 (Excitatory Amino Acid Antagonists)
      0 (LY 341495)
      0 (Xanthenes)
      6384-92-5 (N-Methylaspartate)
      6LR8C1B66Q (Dizocilpine Maleate)
    • الموضوع:
      Date Created: 20141220 Date Completed: 20151221 Latest Revision: 20220129
    • الموضوع:
      20250114
    • الرقم المعرف:
      PMC4272291
    • الرقم المعرف:
      10.1371/journal.pone.0115374
    • الرقم المعرف:
      25526617