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Individual Differences in Impulsive Action Reflect Variation in the Cortical Serotonin 5-HT2A Receptor System
- Source :
- Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 40(8)
- Publication Year :
- 2014
-
Abstract
- Impulsivity is an important feature of multiple neuropsychiatric disorders, and individual variation in the degree of inherent impulsivity could play a role in the generation or exacerbation of problematic behaviors. Serotonin (5-HT) actions at the 5-HT2AR receptor (5-HT2AR) promote and 5-HT2AR antagonists suppress impulsive action (the inability to withhold premature responses; motor impulsivity) upon systemic administration or microinfusion directly into the medial prefrontal cortex (mPFC), a node in the corticostriatal circuit that is thought to play a role in the regulation of impulsive action. We hypothesized that the functional capacity of the 5-HT2AR, which is governed by its expression, localization, and protein/protein interactions (eg, postsynaptic density 95 (PSD95)), may drive the predisposition to inherent impulsive action. Stable high-impulsive (HI) and low-impulsive (LI) phenotypes were identified from an outbred rodent population with the 1-choice serial reaction time (1-CSRT) task. HI rats exhibited a greater head-twitch response following administration of the preferential 5-HT2AR agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) and were more sensitive to the effects of the selective 5-HT2AR antagonist M100907 to suppress impulsive action relative to LI rats. A positive correlation was observed between levels of premature responses and 5-HT2AR binding density in frontal cortex ([(3)H]-ketanserin radioligand binding). Elevated mPFC 5-HT2AR protein expression concomitant with augmented association of the 5-HT2AR with PSD95 differentiated HI from LI rats. The observed differential sensitivity of HI and LI rats to 5-HT2AR ligands and associated distinct 5-HT2AR protein profiles provide evidence that spontaneously occurring individual differences in impulsive action reflect variation in the cortical 5-HT2AR system.
- Subjects :
- Agonist
Male
Ketanserin
medicine.drug_class
Population
Individuality
Prefrontal Cortex
Impulsivity
Tritium
Choice Behavior
Developmental psychology
Rats, Sprague-Dawley
Serotonin Agents
Piperidines
medicine
Reaction Time
Animals
Immunoprecipitation
Receptor, Serotonin, 5-HT2A
Prefrontal cortex
education
Pharmacology
education.field_of_study
Rats
Fluorobenzenes
Psychiatry and Mental health
Dimethoxyphenylethylamine
Head Movements
Impulsive Behavior
Original Article
Serotonin
medicine.symptom
Psychology
Neuroscience
Postsynaptic density
medicine.drug
Protein Binding
Subjects
Details
- ISSN :
- 1740634X
- Volume :
- 40
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
- Accession number :
- edsair.doi.dedup.....595aff83e27e8b42fa1809119f6547b1