Relationship between limbic and cortical 5-HT neurotransmission and acquisition and reversal learning in a go/no-go task in rats

Psychopharmacology (Berl). 2006 Dec;189(2):249-58. doi: 10.1007/s00213-006-0559-0. Epub 2006 Oct 3.


Rationale: Specific brain structures have been suggested to be involved in impulsive responding assessed by a variety of operant tasks. Central serotonin (5-HT) function has also been widely implicated in impulsivity; however, little research has addressed the regional aspect of 5-HT roles in different impulsive indices of task performance.

Objective: We analyzed the relationships between acquisition and reversal learning in a go/no-go task as different behavioral measures of impulsivity and focal concentrations of 5-HT and its metabolites in the brain.

Materials and methods: Rats administered with parachloroamphetamine (PCA) and vehicle were tested in both acquisition and reversal phases in a go/no-go visual discrimination task. Neurochemical analysis was performed to determine 5-HT concentrations in micropunched brain tissues.

Results: PCA administration induced regionally 5-HT depletion in the brain and impaired learning performance in both tests. For both tests, significant negative correlations between learning performance and 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) concentrations were observed in the medial prefrontal cortex (mPFC) and amygdala (Amyg). In contrast, significant negative correlations between learning performance and 5-HT and 5-HIAA concentrations were observed for the orbitofrontal cortex (OFC) exclusively in the reversal learning phase.

Conclusions: The present data indicate that 5-HT neurotransmission to the mPFC and Amyg is involved in inhibitory control over responses to discriminated stimuli associated with the go/no-go paradigm common to both tests. In contrast, 5-HT neurotransmission to the OFC is especially involved in additional processes associated with reversal learning.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / metabolism
  • Amygdala / drug effects
  • Amygdala / metabolism
  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / physiology*
  • Conditioning, Operant / drug effects
  • Conditioning, Operant / physiology
  • Discrimination Learning / drug effects
  • Discrimination Learning / physiology
  • Dopamine / metabolism
  • Feeding Behavior / drug effects
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Hydroxyindoleacetic Acid / metabolism
  • Limbic System / drug effects
  • Limbic System / metabolism
  • Limbic System / physiology*
  • Male
  • Motor Activity / drug effects
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / metabolism
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / metabolism
  • Rats
  • Rats, Wistar
  • Reversal Learning / drug effects
  • Reversal Learning / physiology*
  • Serotonin / metabolism
  • Serotonin / physiology*
  • Serotonin Antagonists / pharmacology
  • Stress, Psychological / psychology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*
  • p-Chloroamphetamine / pharmacology*


  • Serotonin Antagonists
  • 3,4-Dihydroxyphenylacetic Acid
  • Serotonin
  • Hydroxyindoleacetic Acid
  • p-Chloroamphetamine
  • Dopamine