title: Dopamine precursor depletion improves punishment prediction during reversal learning in healthy females but not males.
abstract: BACKGROUND
  The neurotransmitter dopamine has frequently been implicated in reward processing but is also, increasingly, implicated in punishment processing. We have previously shown that both patients with Parkinson's disease and healthy individuals with low dopamine (DA) synthesis are better at reversal learning based on punishment than reward. Here, we extend these prior findings by examining the effects of artificially reducing DA synthesis in healthy individuals performing this previously employed task.
  
  
  METHODS
  In a double-blind, placebo-controlled crossover design, we applied the acute tyrosine and phenylalanine depletion (ATPD) procedure to reduce global DA synthesis in 15 female and 14 male subjects. Each subject performed the reward- and punishment-based reversal-learning paradigm.
  
  
  RESULTS
  There was a significant three-way interaction between ATPD, the valence of the outcome signalling reversal and the gender of the participants. Examination of punishment and reward-based reversals separately revealed that this was driven by a significant improvement in punishment processing in female but not male subjects following DA depletion.
  
  
  CONCLUSIONS
  Reducing DA synthesis in healthy individuals shifted sensitivity of performance from reward to punishment processing. Gender differences in DA synthesis might underlie the selectivity of this effect to female subjects. Such gender biases may go some way towards explaining the gender biases in certain psychiatric disorders such as depression and Parkinson's disease.
authors.affiliation: Department of Psychiatry and Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, Addenbrooke's Hospital, P.O. Box 189, Level E4, Hills Road, Cambridge, CB2 2QQ, UK. oliver.j.robinson@googlemail.com
authors.forename: Oliver J
authors.initials: OJ
authors.lastname: Robinson
authors.forename: Holly R
authors.initials: HR
authors.lastname: Standing
authors.forename: Elise E
authors.initials: EE
authors.lastname: DeVito
authors.forename: Roshan
authors.initials: R
authors.lastname: Cools
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Sahakian
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D004298:Dopamine / Q000096:biosynthesis / Q000378:metabolism*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010649:Phenylalanine / Q000172:deficiency; D011678:Punishment; D012193:Reversal Learning; D012201:Reward; D012737:Sex Factors; D014443:Tyrosine / Q000172:deficiency; D055815:Young Adult
chemical_list: D014443:Tyrosine; D010649:Phenylalanine; D004298:Dopamine