Document Detail


Dissociable effects of selective 5-HT2A and 5-HT2C receptor antagonists on serial spatial reversal learning in rats.
MedLine Citation:
PMID:  17957219     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Serotonin (5-hydroxytryptamine, or 5-HT) is strongly implicated in the ability to shift behavior in response to changing stimulus-reward contingencies. However, there is little information on the contribution of different 5-HT receptors in reversal learning. Thus, we investigated the effects of systemic administration of the 5-HT(2A) antagonist M100907 (0, 0.01, 0.03, and 0.1 mg/kg, i.p.) and the 5-HT(2C) antagonist SB 242084 (0, 0.1, 0.3, and 1.0 mg/kg, i.p.) on the performance of an instrumental two-lever spatial discrimination and serial spatial reversal learning task, where both levers were presented and only one was reinforced. The rat was required to respond on the reinforced lever under a fixed ratio 3 schedule of reinforcement. Following attainment of criterion, a series of within-session reversals was presented. Neither M100907 nor SB 242084 altered performance during spatial discrimination and retention of the previously reinforced contingencies. M100907 significantly impaired reversal learning by increasing both trials to criterion (only at the highest dose) and incorrect responses to criterion in Reversal 1, a pattern of behavior manifested as increased perseverative responding on the previously reinforced lever. In contrast, SB 242084 improved reversal learning by decreasing trials and incorrect responses to criterion in Reversal 1, with significantly fewer perseverative responses. These data support the view that 5-HT(2A) and 5-HT(2C) receptors have distinct roles in cognitive flexibility and response inhibition. The improved performance in reversal learning observed following 5-HT(2C) receptor antagonism suggests these receptors may offer the potential for therapeutic advances in a number of neuropsychiatric disorders where cognitive deficits are a feature, including obsessive-compulsive disorder.
Authors:
Vasileios Boulougouris; Jeffrey C Glennon; Trevor W Robbins
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-10-24
Journal Detail:
Title:  Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology     Volume:  33     ISSN:  0893-133X     ISO Abbreviation:  Neuropsychopharmacology     Publication Date:  2008 Jul 
Date Detail:
Created Date:  2008-06-12     Completed Date:  2008-09-02     Revised Date:  2011-05-18    
Medline Journal Info:
Nlm Unique ID:  8904907     Medline TA:  Neuropsychopharmacology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2007-19     Citation Subset:  IM    
Affiliation:
Department of Experimental Psychology, Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK. vb257@cam.ac.uk
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MeSH Terms
Descriptor/Qualifier:
Aminopyridines / pharmacology
Animals
Cognition / drug effects
Conditioning, Operant / drug effects
Discrimination Learning / drug effects
Fluorobenzenes / pharmacology
Indoles / pharmacology
Male
Piperidines / pharmacology
Psychomotor Performance / drug effects
Rats
Receptor, Serotonin, 5-HT2A / drug effects*
Receptor, Serotonin, 5-HT2C / drug effects*
Reinforcement Schedule
Reversal Learning / drug effects*
Serotonin Antagonists / pharmacology*
Space Perception / drug effects*
Grant Support
ID/Acronym/Agency:
//Wellcome Trust
Chemical
Reg. No./Substance:
0/6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline; 0/Aminopyridines; 0/Fluorobenzenes; 0/Indoles; 0/Piperidines; 0/Receptor, Serotonin, 5-HT2A; 0/Receptor, Serotonin, 5-HT2C; 0/Serotonin Antagonists; 139290-65-6/MDL 100907

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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