1. Serotonin (5-HT) 5-HT2A Receptor (5-HT2AR):5-HT2CR Imbalance in Medial Prefrontal Cortex Associates with Motor Impulsivity.
- Author
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Anastasio NC, Stutz SJ, Fink LH, Swinford-Jackson SE, Sears RM, DiLeone RJ, Rice KC, Moeller FG, and Cunningham KA
- Subjects
- Animals, Animals, Outbred Strains, Choice Behavior drug effects, Choice Behavior physiology, Executive Function drug effects, Executive Function physiology, Fluorobenzenes pharmacology, Gene Knockdown Techniques, Impulsive Behavior drug effects, Male, Membrane Glycoproteins, Motor Activity drug effects, Neuropsychological Tests, Phenotype, Piperidines pharmacology, Prefrontal Cortex drug effects, Rats, Sprague-Dawley, Receptor, Serotonin, 5-HT2C genetics, Receptors, Interleukin-1, Serotonin Antagonists pharmacology, Synaptosomes drug effects, Synaptosomes metabolism, Impulsive Behavior physiology, Motor Activity physiology, Prefrontal Cortex metabolism, Receptor, Serotonin, 5-HT2A metabolism, Receptor, Serotonin, 5-HT2C metabolism
- Abstract
A feature of multiple neuropsychiatric disorders is motor impulsivity. Recent studies have implicated serotonin (5-HT) systems in medial prefrontal cortex (mPFC) in mediating individual differences in motor impulsivity, notably the 5-HT2AR receptor (5-HT2AR) and 5-HT2CR. We investigated the hypothesis that differences in the ratio of 5-HT2AR:5-HT2CR protein expression in mPFC would predict the individual level of motor impulsivity and that the engineered loss of the 5-HT2CR would result in high motor impulsivity concomitant with elevated 5-HT2AR expression and pharmacological sensitivity to the selective 5-HT2AR antagonist M100907. High and low impulsive rats were identified in a 1-choice serial reaction time task. Native protein levels of the 5-HT2AR and the 5-HT2CR predicted the intensity of motor impulsivity and the 5-HT2AR:5-HT2CR ratio in mPFC positively correlated with levels of premature responses in individual outbred rats. The possibility that the 5-HT2AR and 5-HT2CR act in concert to control motor impulsivity is supported by the observation that high phenotypic motor impulsivity associated with a diminished mPFC synaptosomal 5-HT2AR:5-HT2CR protein:protein interaction. Knockdown of mPFC 5-HT2CR resulted in increased motor impulsivity and triggered a functional disruption of the local 5-HT2AR:5-HT2CR balance as evidenced by a compensatory upregulation of 5-HT2AR protein expression and a leftward shift in the potency of M100907 to suppress impulsive behavior. We infer that there is an interactive relationship between the mPFC 5-HT2AR and 5-HT2CR, and that a 5-HT2AR:5-HT2CR imbalance may be a functionally relevant mechanism underlying motor impulsivity.
- Published
- 2015
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