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

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.