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  • Title: Dorsal-striatal 5-HT₂A and 5-HT₂C receptors control impulsivity and perseverative responding in the 5-choice serial reaction time task.
    Author: Agnoli L, Carli M.
    Journal: Psychopharmacology (Berl); 2012 Jan; 219(2):633-45. PubMed ID: 22113450.
    Abstract:
    RATIONAL: 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. OBJECTIVE: The present study investigated which 5-HT(2A) and 5-HT(2C) 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-HT(2A) antagonist M100907 and 1 and 3 μg/μl doses of 5-HT(2C) 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. CONCLUSIONS: It is suggested that in the dorsal striatum, 5-HT by an action on 5-HT(2A) and 5-HT(2C) receptors may integrate the glutamate corticostriatal inputs critical for different aspects of the 5-CSRT task performance.
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