Psychopharmacology

, Volume 219, Issue 2, pp 633–645 | Cite as

Dorsal–striatal 5-HT2A and 5-HT2C receptors control impulsivity and perseverative responding in the 5-choice serial reaction Time Task

Original Investigation

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-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.

Conclusions

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.

Keywords

5-HT2A receptor 5-HT2C receptor Dorsal striatum Prefrontal cortex NMDA receptor Attention Rat 

Supplementary material

213_2011_2581_MOESM1_ESM.doc (49 kb)
Fig. S1Effects of injection of M100907 in the ventral tegmental area (VTA) alone or in combination with injection of CPP in the medial region of the prefrontal cortex (mPFC) on perseverative responses in the 5-CSRT task. Rats were implanted with bilateral 23-gauge stainless steel guide cannulae in the VTA placed at coordinates: AP +4.2, L ±0.8 and V +1.6 from interaural zero line with the incisor bar set at −3.3 relative to interaural line (Paxinos and Watson 1986). Additional bilateral cannulae were implanted in the mPFC at coordinates: AP +3.8; L ±0.7 from bregma and V −3.2 from dura (Paxinos and Watson 1986). In the VTA, 20 ng/0.2 μl M100907 (M) or 0.2 μl vehicle (V) was injected, 5 min before an intra-mPFC injection of vehicle 1 μl (V) or 50 ng/μl CPP (CPP). Rats were tested 10 min after receiving CPP. The order of injections was according to a Latin square design with an interval of 2 days between treatments. The histograms represent the mean ± SEM of six rats. A two-way within subjects ANOVA showed a significant interaction M × CPP (F1,15=14.01 P=0.002). *P<0.05 vs. V + V; #P<0.05 vs. V + CPP; Tukey's test (DOC 49 kb)

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  1. 1.Department of NeuroscienceIstituto di Ricerche Farmacologiche “Mario Negri”MilanItaly

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