title: Role of Central Serotonin in Anticipation of Rewarding and Punishing Outcomes: Effects of Selective Amygdala or Orbitofrontal 5-HT Depletion.
abstract: Understanding the role of serotonin (or 5-hydroxytryptamine, 5-HT) in aversive processing has been hampered by the contradictory findings, across studies, of increased sensitivity to punishment in terms of subsequent response choice but decreased sensitivity to punishment-induced response suppression following gross depletion of central 5-HT. To address this apparent discrepancy, the present study determined whether both effects could be found in the same animals by performing localized 5-HT depletions in the amygdala or orbitofrontal cortex (OFC) of a New World monkey, the common marmoset. 5-HT depletion in the amygdala impaired response choice on a probabilistic visual discrimination task by increasing the effectiveness of misleading, or false, punishment and reward, and decreased response suppression in a variable interval test of punishment sensitivity that employed the same reward and punisher. 5-HT depletion in the OFC also disrupted probabilistic discrimination learning and decreased response suppression. Computational modeling of behavior on the discrimination task showed that the lesions reduced reinforcement sensitivity. A novel, unitary account of the findings in terms of the causal role of 5-HT in the anticipation of both negative and positive motivational outcomes is proposed and discussed in relation to current theories of 5-HT function and our understanding of mood and anxiety disorders.
authors.affiliation: Department of Psychology, University of Cambridge, Cambridge CB2 3EB, UK Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge CB2 3EB, UK Current Address: Affective Cognitive Neuroscience Laboratory, Department of Behavioral Neurobiology and Drug Development, Institute of Pharmacology Polish Academy of Sciences, ul Smetna 12, 31-343 Krakow, Poland.
authors.forename: Rafal
authors.initials: R
authors.lastname: Rygula
authors.affiliation: Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge CB2 3EB, UK Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3DY, UK.
authors.forename: Hannah F
authors.initials: HF
authors.lastname: Clarke
authors.affiliation: Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge CB2 3EB, UK Department of Psychiatry, University of Cambridge, School of Clinical Medicine, Cambridge CB2 0QQ, UK Liaison Psychiatry Service, Cambridgeshire and Peterborough NHS Foundation Trust, Box 190, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
authors.forename: Rudolf N
authors.initials: RN
authors.lastname: Cardinal
authors.affiliation: Department of Psychology, University of Cambridge, Cambridge CB2 3EB, UK Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge CB2 3EB, UK.
authors.forename: Gemma J
authors.initials: GJ
authors.lastname: Cockcroft
authors.affiliation: Department of Psychology, University of Cambridge, Cambridge CB2 3EB, UK Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge CB2 3EB, UK.
authors.forename: Jing
authors.initials: J
authors.lastname: Xia
authors.affiliation: Department of Psychology, University of Cambridge, Cambridge CB2 3EB, UK Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge CB2 3EB, UK.
authors.forename: Jeff W
authors.initials: JW
authors.lastname: Dalley
authors.affiliation: Department of Psychology, University of Cambridge, Cambridge CB2 3EB, UK Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge CB2 3EB, UK.
authors.forename: Trevor W
authors.initials: TW
authors.lastname: Robbins
authors.affiliation: Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge CB2 3EB, UK Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3DY, UK.
authors.forename: Angela C
authors.initials: AC
authors.lastname: Roberts
mesh_terms: D015116:5,7-Dihydroxytryptamine / Q000633:toxicity; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D002144:Callithrix; D004192:Discrimination, Psychological; D005260:Female; D008297:Male; D009042:Motivation / Q000502:physiology*; D010775:Photic Stimulation; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D011336:Probability; D011678:Punishment; D021641:Recognition, Psychology; D012153:Retention, Psychology / Q000502:physiology; D012201:Reward; D012701:Serotonin / Q000172:deficiency*; D018490:Serotonin Agents / Q000633:toxicity
chemical_list: D018490:Serotonin Agents; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin
keywords: amygdala; marmoset; orbitofrontal cortex; probabilistic reversal learning