title: Ketamine decreases sensitivity of male rats to misleading negative feedback in a probabilistic reversal-learning task.
abstract: Depression is characterized by an excessive attribution of value to negative feedback. This imbalance in feedback sensitivity can be measured using the probabilistic reversal-learning (PRL) task. This task was initially designed for clinical research, but introduction of its rodent version provides a new and much needed translational paradigm to evaluate potential novel antidepressants.
  
  
  
  In the present study, we aimed at evaluating the effects of a compound showing clear antidepressant properties-ketamine (KET)-on the sensitivity of rats to positive and negative feedback in the PRL paradigm.
  
  
  
  We trained healthy rats in an operant version of the PRL task. For successful completion of the task, subjects had to learn to ignore infrequent and misleading feedback, arising from the probabilistic (80:20) nature of the discrimination. Subsequently, we evaluated the effect of KET (5, 10, and 20 mg/kg) on feedback sensitivity 1, 24, and 48 h after administration.
  
  
  
  We report that acute administration of the highest dose of KET (20 mg/kg) rapidly and persistently decreases the proportion of lose-shift responses made by rats after receiving negative feedback.
  
  
  
  Present results suggest that KET decreases negative feedback sensitivity and that changes in this basic neurocognitive function might be one of the factors responsible for its antidepressant action.
authors.affiliation: Institute of Pharmacology, Polish Academy of Sciences, Department of Behavioral Neuroscience and Drug Development, Affective Cognitive Neuroscience Laboratory, 12 Smetna Street, 31-343, Krakow, Poland.
authors.forename: Michal
authors.initials: M
authors.lastname: Rychlik
authors.affiliation: Institute of Pharmacology, Polish Academy of Sciences, Department of Behavioral Neuroscience and Drug Development, Affective Cognitive Neuroscience Laboratory, 12 Smetna Street, 31-343, Krakow, Poland.
authors.forename: Eva
authors.initials: E
authors.lastname: Bollen
authors.affiliation: Institute of Pharmacology, Polish Academy of Sciences, Department of Behavioral Neuroscience and Drug Development, Affective Cognitive Neuroscience Laboratory, 12 Smetna Street, 31-343, Krakow, Poland. rygula@gmail.com.
authors.forename: Rafal
authors.initials: R
authors.lastname: Rygula
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012193:Reversal Learning / Q000187:drug effects*
chemical_list: D000928:Antidepressive Agents; D007649:Ketamine
keywords: Animal model; Feedback sensitivity; Ketamine; Probabilistic reversal learning; Rat