title: Dissociating the cognitive effects of levodopa versus dopamine agonists in a neurocomputational model of learning in Parkinson's disease.
abstract: OBJECTIVE
  Levodopa and dopamine agonists have different effects on the motor, cognitive, and psychiatric aspects of Parkinson's disease (PD).
  
  
  METHODS
  Using a computational model of basal ganglia (BG) and prefrontal cortex (PFC) dopamine, we provide a theoretical synthesis of the dissociable effects of these dopaminergic medications on brain and cognition. Our model incorporates the findings that levodopa is converted by dopamine cells into dopamine, and thus activates prefrontal and striatal D(1) and D(2) dopamine receptors, whereas antiparkinsonian dopamine agonists directly stimulate D(2) receptors in the BG and PFC (although some have weak affinity to D(1) receptors).
  
  
  RESULTS
  In agreement with prior neuropsychological studies, our model explains how levodopa enhances, but dopamine agonists impair or have no effect on, stimulus-response learning and working memory.
  
  
  CONCLUSIONS
  Our model explains how levodopa and dopamine agonists have differential effects on motor and cognitive processes in PD.
authors.affiliation: Marcs Institute for Brain and Behaviour and Foundational Processes of Behaviour, School of Social Sciences and Psychology, University of Western Sydney, Sydney, N.S.W., Australia. a.moustafa@uws.edu.au
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: Moustafa
authors.forename: Mohammad M
authors.initials: MM
authors.lastname: Herzallah
authors.forename: Mark A
authors.initials: MA
authors.lastname: Gluck
mesh_terms: D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects / Q000502:physiology; D003071:Cognition / Q000187:drug effects* / Q000502:physiology; D018491:Dopamine Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000502:physiology; D006801:Humans; D007858:Learning / Q000187:drug effects* / Q000502:physiology; D007980:Levodopa / Q000494:pharmacology* / Q000627:therapeutic use; D008568:Memory / Q000187:drug effects / Q000502:physiology; D008959:Models, Neurological; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology; D017447:Receptors, Dopamine D1 / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology
chemical_list: D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D018698:Glutamic Acid; D007980:Levodopa; D005680:gamma-Aminobutyric Acid