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 language | English |
|---|---|
| Pages (from-to) | 633-645 |
| Number of pages | 13 |
| Journal | Psychopharmacology |
| Volume | 219 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Jan 2012 |
Fingerprint
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 journal › Article
}
TY - JOUR
T1 - Dorsal-striatal 5-HT 2A and 5-HT 2C receptors control impulsivity and perseverative responding in the 5-choice serial reaction Time Task
AU - Agnoli, Laura
AU - Carli, Mirjana
PY - 2012/1
Y1 - 2012/1
N2 - 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.
AB - 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.
KW - 5-HT receptor
KW - 5-HT receptor
KW - Attention
KW - Dorsal striatum
KW - NMDA receptor
KW - Prefrontal cortex
KW - Rat
UR - http://www.scopus.com/inward/record.url?scp=84856686440&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84856686440&partnerID=8YFLogxK
U2 - 10.1007/s00213-011-2581-0
DO - 10.1007/s00213-011-2581-0
M3 - Article
C2 - 22113450
AN - SCOPUS:84856686440
VL - 219
SP - 633
EP - 645
JO - Psychopharmacology
JF - Psychopharmacology
SN - 0033-3158
IS - 2
ER -