Serotonergic modulation of attentional processes in the rat prefrontal cortex

Abstract

The experimental evidence for the 5-HT system involvement in cognitive processes sensitive to dysfunction of the prefrontal cortex is sparse. The aim of this project was to examine serotonergic modulation of attentional performance deficits in the 5- choice serial reaction time (5-CSRT) task induced by blockade of NMDA receptors in the medial prefrontal cortex (mPFC) of rats. Using in-vivo microdialysis techniques attempts have been made to relate the behavioural effects of 5-HT receptors agonists and antagonists to changes in glutamate and 5-HT efflux induced by blockade of NMDA receptors in the mPFC. The data clearly demonstrate that glutamate transmission in the mPFC is involved in the control of attentional performance on the 5-CSRT task. The data also show for the first time that enhanced glutamate and 5-HT release induced by blockade of NMDA receptors in the mPFC are not causally related to aspects of inhibitory response control as indexed by impulsive anticipatory and compulsive perseverative responses. The important suggestion emerging from this study is that of distinct neuromodulation in the control of impulsive responding by 5-HT 2A/5-HT2C receptors and in compulsive behaviours by 5-HT1A and DA D 2 receptors in the prefrontal cortex. Intriguingly deficits in attentional accuracy might be associated with increased glutamate release in the mPFC. Thus behavioural evidence obtained in animals with dysfunctional glutamate transmission performing the 5-CSRT task, as well as a series of pharmacological manipulations of 5-HT, DA and mGlu2/3 receptor mechanisms have been presented that are consistent with the hypothesis that serotonergic mechanisms in the prefrontal cortex play specific roles in attention and response selection particularly when these have a possible function in the strategic control of behaviour. These behavioural and neurochemical studies provide new information on the physiological mechanisms involved in the control of various aspects of attentional performance as well as in cognitive deficits associated with some neuropsychiatric disorders.