title: Monoamine levels within the orbitofrontal cortex and putamen interact to predict reversal learning performance.
abstract: BACKGROUND
  The compulsive and inflexible behaviors that are present in many psychiatric disorders, particularly behavioral addictions and obsessive-compulsive disorder, may be due to neurochemical dysfunction within the circuitry that enables goal-directed behaviors. Experimental removal of serotonin or dopamine within the orbitofrontal cortex or dorsal striatum, respectively, impairs flexible responding in a reversal learning test, suggesting that these neurochemical systems exert important modulatory influences on goal-directed behaviors. Nevertheless, the behavioral impairments present in psychiatric disorders are likely due to subtle neurochemical differences, and it remains unknown whether naturally occurring variation in neurochemical levels associate with individual differences in flexible, reward-directed behaviors.
  
  
  METHODS
  The current study assessed the ability of 24 individual juvenile monkeys to acquire, retain, and reverse discrimination problems and examined whether monoamine levels in the orbitofrontal cortex, caudate nucleus, and putamen could explain variance in behavior.
  
  
  RESULTS
  The interaction between dopamine levels in the putamen and serotonin levels in the orbitofrontal cortex explained 61% of the variance in a measure of behavioral flexibility but not measures of associative learning or memory. The interaction mirrored that of a hyperbolic function, with reversal learning performance being poorest in either monkeys with relatively low levels of orbitofrontal serotonin and putamen dopamine or in monkeys with relatively high levels of orbitofrontal serotonin and putamen dopamine levels.
  
  
  CONCLUSIONS
  These results support the hypothesis that subcortical and cortical neuromodulatory systems interact to guide aspects of goal-directed behavior, providing insight into the neurochemical dysfunction that may underlie the inflexible and compulsive behaviors present in psychiatric disorders.
authors: Department of Psychology, University of California, Los Angeles, CA 90095-1563, USA.
authors: Stephanie M
authors: SM
authors: Groman
authors: Alex S
authors: AS
authors: James
authors: Emanuele
authors: E
authors: Seu
authors: Maverick A
authors: MA
authors: Crawford
authors: Sandra N
authors: SN
authors: Harpster
authors: James David
authors: JD
authors: Jentsch
mesh_terms: D000818:Animals; D002421:Caudate Nucleus / Q000378:metabolism / Q000502:physiology; D002522:Chlorocebus aethiops; D004193:Discrimination Learning / Q000502:physiology; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D005625:Frontal Lobe / Q000378:metabolism / Q000502:physiology*; D008297:Male; D011699:Putamen / Q000378:metabolism / Q000502:physiology*; D012193:Reversal Learning / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*
chemical_list: D012701:Serotonin; D004298:Dopamine