title: Tryptophan depletion impairs stimulus-reward learning while methylphenidate disrupts attentional control in healthy young adults: implications for the monoaminergic basis of impulsive behaviour.
abstract: BACKGROUND
  Altered serotonergic and dopaminergic function have been widely implicated in behavioural disorders associated with impulsivity and risk-taking. However, little research has addressed the specific cognitive consequences of changed monoaminergic function that might contribute to the production of impulsive behaviour.
  
  
  OBJECTIVE
  We compared the effects of rapid plasma tryptophan depletion, acute doses of the mixed indirect catecholamine agonist, methylphenidate (40 mg), and acute doses of the alpha(1)/alpha(2 )agonist, clonidine (1.5 microg/kg), on aspects of visual discrimination learning involving either acquisition of altered stimulus-reward associations (i.e. updating the affective valence of exteroceptive stimuli) or the control of attention towards relevant as opposed to irrelevant stimulus dimensions.
  
  
  RESULTS
  Relative to subjects who received placebo, subjects with reduced tryptophan exhibited a deficit in the ability to learn changed stimulus-reward associations, but were still able to shift an acquired attentional set away from a now-irrelevant stimulus dimension towards a newly relevant dimension. By contrast, subjects who received methylphenidate were able to learn effectively about changing stimulus-reward associations, but showed an enhanced ability to shift an attentional bias, in combination with slowed response times. Subjects who received clonidine showed neither of these changes.
  
  
  CONCLUSIONS
  These results suggest that reduction in central serotonin leads to altered neuromodulation of the cortical and subcortical regions (e.g. orbitofrontal cortex, striatum and anterior temporal structures) that mediate important aspects of associative learning whereby exteroceptive stimuli acquire altered incentive motivational value. On the other hand, facilitation of catecholamine neurotransmitters may disrupt the allocation of attention between relevant and irrelevant features of the environment, perhaps through altered modulation of the dorsolateral prefrontal cortex. The implications of these results for understanding the differential neuromodulation of cognitive functions are discussed.
authors.affiliation: Departments of Experimental Psychology and Psychiatry, University of Cambridge, Cambridge, UK. robert.rogers@psychiatry.oxford.ac.uk
authors.forename: R D
authors.initials: RD
authors.lastname: Rogers
authors.forename: A J
authors.initials: AJ
authors.lastname: Blackshaw
authors.forename: H C
authors.initials: HC
authors.lastname: Middleton
authors.forename: K
authors.initials: K
authors.lastname: Matthews
authors.forename: K
authors.initials: K
authors.lastname: Hawtin
authors.forename: C
authors.initials: C
authors.lastname: Crowley
authors.forename: A
authors.initials: A
authors.lastname: Hopwood
authors.forename: C
authors.initials: C
authors.lastname: Wallace
authors.forename: J F
authors.initials: JF
authors.lastname: Deakin
authors.forename: B J
authors.initials: BJ
authors.lastname: Sahakian
authors.forename: T W
authors.initials: TW
authors.lastname: Robbins
mesh_terms: D000293:Adolescent; D018663:Adrenergic Agents / Q000494:pharmacology*; D000328:Adult; D001288:Attention / Q000187:drug effects*; D003000:Clonidine / Q000494:pharmacology*; D004193:Discrimination Learning / Q000187:drug effects*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007175:Impulsive Behavior; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology*; D012201:Reward; D014364:Tryptophan / Q000097:blood* / Q000187:drug effects
chemical_list: D018663:Adrenergic Agents; D008774:Methylphenidate; D014364:Tryptophan; D003000:Clonidine