Intra-prefrontal S-OH-DPAT and M100907 improve visuospatial attention and decrease impulsivity on the five-choice serial reaction time task in rats

Rationale: The central serotonergic systems are a major, target for drugs used to treat neuropsychiatric disorders such as depression and schizophrenia in which disruption of frontal cortex function has been implicated. However, it is not known precisely how serotonin (5-HT) modulates the medial prefrontal cortex (mPFC) to affect cognitive function and behaviour. Objective: To investigate the roles of 5-HT1A and 5-HT2A receptors in mPFC on performance of the five-choice serial reaction time task (5CSRT), which assesses visuospatial attention, impulsivity and motivational processes. Methods: Following training on the 5CSRT, rats were implanted with bilateral guide cannulae aimed at the mPFC.. Rats received intra-mPFC infusions of either 8-OH-DPAT (10, 30 and 100 ng) or M100907 (30, 100 and 300 ng) according to a Latin square design. Results: Both 8-OH-DPAT and M100907 selectively enhanced accuracy of target detection. When the stimulus duration was shortened, infusions of 8-OH-DPAT continued to improve accuracy, whereas M100907 decreased premature responding and omissions, thus partly dissociating the effects of these two compounds. Similar effects were obtained following systemic administration of M100907 and 8-OH-DPAT. The effects of 8-OH-DPAT were blocked by the 5-HT1A antagonist WAY 100635, at a dose that itself had no significant effects on behaviour. Conclusions: These results indicate that modulation of 5-HT function within the mPFC via distinct receptors can enhance performance on the 5CSRT. These findings suggest a mechanism by which serotonergic agents improve cognitive function, which may be relevant to their therapeutic benefit in the treatment of neuropsychiatric disorders.