title: Positive and negative feedback learning and associated dopamine and serotonin transporter binding after methamphetamine.
abstract: Learning from mistakes and prospectively adjusting behavior in response to reward feedback is an important facet of performance monitoring. Dopamine (DA) pathways play an important role in feedback learning and a growing literature has also emerged on the importance of serotonin (5HT) in reward learning, particularly during punishment or reward omission (negative feedback). Cognitive impairments resulting from psychostimulant exposure may arise from altered patterns in feedback learning, which in turn may be modulated by DA and 5HT transmission. We analyzed long-term, off-drug changes in learning from positive and negative feedback and associated striatal DA transporter (DAT) and frontocortical 5HT transporter (SERT) binding in rats pretreated with methamphetamine (mAMPH). Specifically, we assessed the reversal phase of pairwise visual discrimination learning in rats receiving single dose- (mAMPHsingle) vs. escalating-dose exposure (mAMPHescal). Using fine-grained trial-by-trial analyses, we found increased sensitivity to and reliance on positive feedback in mAMPH-pretreated animals, with the mAMPHsingle group showing more pronounced use of this type of feedback. In contrast, overall negative feedback sensitivity was not altered following any mAMPH treatment. In addition to validating the enduring effects of mAMPH on early reversal learning, we found more consecutive error commissions before the first correct response in mAMPH-pretreated rats. This behavioral rigidity was negatively correlated with subregional frontocortical SERT whereas positive feedback sensitivity negatively correlated with striatal DAT binding. These results provide new evidence for the overlapping, yet dissociable roles of DA and 5HT systems in overcoming perseveration and in learning new reward rules.
authors: University of California, Los Angeles, CA 90095, USA.
authors: Alexandra
authors: A
authors: Stolyarova
authors: University of California, Irvine, CA 92617, USA.
authors: Steve J
authors: SJ
authors: O'Dell
authors: University of California, Irvine, CA 92617, USA.
authors: John F
authors: JF
authors: Marshall
authors: University of California, Los Angeles, CA 90095, USA. Electronic address: aizquie@psych.ucla.edu.
authors: Alicia
authors: A
authors: Izquierdo
mesh_terms: D000818:Animals; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004193:Discrimination Learning / Q000187:drug effects*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D005246:Feedback / Q000187:drug effects; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D012193:Reversal Learning / Q000187:drug effects*; D012201:Reward; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*
chemical_list: D000697:Central Nervous System Stimulants; D050483:Dopamine Plasma Membrane Transport Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; D008694:Methamphetamine
keywords: Caudate-putamen; Cingulate cortex; Dopamine; Orbitofrontal cortex; Reversal learning; Serotonin