Dorsal–striatal 5-HT2A and 5-HT2C receptors control impulsivity and perseverative responding in the 5-choice serial reaction Time Task
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Prefrontal cortex (PFC) and dorsal striatum are part of the neural circuit critical for executive attention. The relationship between 5-HT and aspects of attention and executive control is complex depending on experimental conditions and the level of activation of different 5-HT receptors within the nuclei of corticostriatal circuitry.
The present study investigated which 5-HT2A and 5-HT2C receptors in the dorsomedial-striatum (dm-STR) contribute to executive attention deficit induced by blockade of NMDA receptors in the PFC.
Materials and results
Executive attention was assessed by the five-choice serial reaction time task (5-CSRTT), which provides indices of attention (accuracy) and those of executive control over performance such as premature (an index of impulsivity) and perseverative responding. The effects of targeted infusion in dm-STR of 100 and 300 ng/μl doses of the selective 5-HT2A antagonist M100907 and 1 and 3 μg/μl doses of 5-HT2C agonist Ro60-0175 was examined in animals injected with 50 ng/μl dose of a competitive NMDA receptor antagonist 3-(R)-2-carboxypiperazin-4-phosphonic acid (CPP) in the mPFC. Blockade of NMDA receptors impaired accuracy as well as executive control as shown by increased premature and perseverative responding. The CPP-induced premature and perseverative over-responding were dose-dependently prevented by both M100907 and Ro60-0175. Both drugs partially removed the CPP-induced accuracy deficit but only at the highest dose tested.
It is suggested that in the dorsal striatum, 5-HT by an action on 5-HT2A and 5-HT2C receptors may integrate the glutamate corticostriatal inputs critical for different aspects of the 5-CSRT task performance.
Keywords5-HT2A receptor 5-HT2C receptor Dorsal striatum Prefrontal cortex NMDA receptor Attention Rat
We thank Prof. Trevor W Robbins and Dr Roberto W. Invernizzi for their helpful discussion of these studies. Laura Agnoli was a recipient of a fellowship of the Monzino Foundation, Milan, Italy.
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