Dorsal-striatal 5-HT 2A and 5-HT 2C receptors control impulsivity and perseverative responding in the 5-choice serial reaction Time Task

Laura Agnoli, Mirjana Carli

Research output: Contribution to journalArticle

26 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)633-645
Number of pages13
JournalPsychopharmacology
Volume219
Issue number2
DOIs
Publication statusPublished - Jan 2012

Fingerprint

Receptor, Serotonin, 5-HT2C
Corpus Striatum
Impulsive Behavior
Reaction Time
Serotonin
Executive Function
N-Methyl-D-Aspartate Receptors
Prefrontal Cortex
Serotonin Receptor Agonists
Serotonin Antagonists
Serotonin Receptors
Task Performance and Analysis
Glutamic Acid
Pharmaceutical Preparations
phosphonic acid

Keywords

  • 5-HT receptor
  • 5-HT receptor
  • Attention
  • Dorsal striatum
  • NMDA receptor
  • Prefrontal cortex
  • Rat

ASJC Scopus subject areas

  • Pharmacology

Cite this

Dorsal-striatal 5-HT 2A and 5-HT 2C receptors control impulsivity and perseverative responding in the 5-choice serial reaction Time Task. / Agnoli, Laura; Carli, Mirjana.

In: Psychopharmacology, Vol. 219, No. 2, 01.2012, p. 633-645.

Research output: Contribution to journalArticle

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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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