Serotonin (5-hydroxytryptamine) 5-HT2A receptor: Association with inherent and cocaine-evoked behavioral disinhibition in rats

Noelle Anastasio, Erin C. Stoffel, Robert G. Fox, Marcy J. Bubar, Kenner C. Rice, Frederick G. Moeller, Kathryn Cunningham

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Alterations in the balance of functional activity within the serotonin [5-hydroxytryptamine (5-HT)] system are hypothesized to underlie impulse control. Cocaine-dependent subjects consistently show greater impulsivity relative to nondrug using control subjects. Preclinical studies suggest that the 5-HT2A receptor (5-HT2AR) contributes to the regulation of impulsive behavior and also mediates some of the behavioral effects of cocaine. We hypothesized that the selective 5-HT2AR antagonist M100907 would reduce inherent levels of impulsivity and attenuate impulsive responding induced by cocaine in two animal models of impulsivity, the differential reinforcement of low rate (DRL) task and the one-choice serial reaction time (1-CSRT) task. M100907 reduced rates of responding in the DRL task and premature responding in the 1-CSRT task. Conversely, cocaine disrupted rates of responding in the DRL task and increased premature responding in the 1-CSRT task. M100907 attenuated cocaine-induced increases in specific markers of behavioral disinhibition in the DRL and 1-CSRT tasks. These results suggest that the 5-HT2AR regulates inherent impulsivity, and that blockade of the 5-HT2AR alleviates specific aspects of elevated levels of impulsivity induced by cocaine exposure. These data point to the 5-HT 2AR as an important regulatory substrate in impulse control.

Original languageEnglish (US)
Pages (from-to)248-261
Number of pages14
JournalBehavioural Pharmacology
Volume22
Issue number3
DOIs
StatePublished - Jun 2011

Fingerprint

Receptor, Serotonin, 5-HT2A
Impulsive Behavior
Cocaine
Serotonin
Serotonin 5-HT2 Receptor Antagonists
Reaction Time
serotonin 5 receptor
Animal Models
Reinforcement (Psychology)
MDL 100907

Keywords

  • 5-HT receptor
  • behavioral disinhibition
  • cocaine
  • differential reinforcement of low rate task
  • impulsivity
  • one-choice serial reaction time task
  • rat

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

Cite this

Serotonin (5-hydroxytryptamine) 5-HT2A receptor : Association with inherent and cocaine-evoked behavioral disinhibition in rats. / Anastasio, Noelle; Stoffel, Erin C.; Fox, Robert G.; Bubar, Marcy J.; Rice, Kenner C.; Moeller, Frederick G.; Cunningham, Kathryn.

In: Behavioural Pharmacology, Vol. 22, No. 3, 06.2011, p. 248-261.

Research output: Contribution to journalArticle

Anastasio, Noelle ; Stoffel, Erin C. ; Fox, Robert G. ; Bubar, Marcy J. ; Rice, Kenner C. ; Moeller, Frederick G. ; Cunningham, Kathryn. / Serotonin (5-hydroxytryptamine) 5-HT2A receptor : Association with inherent and cocaine-evoked behavioral disinhibition in rats. In: Behavioural Pharmacology. 2011 ; Vol. 22, No. 3. pp. 248-261.
@article{79667506a42941f4950e035665bdf42e,
title = "Serotonin (5-hydroxytryptamine) 5-HT2A receptor: Association with inherent and cocaine-evoked behavioral disinhibition in rats",
abstract = "Alterations in the balance of functional activity within the serotonin [5-hydroxytryptamine (5-HT)] system are hypothesized to underlie impulse control. Cocaine-dependent subjects consistently show greater impulsivity relative to nondrug using control subjects. Preclinical studies suggest that the 5-HT2A receptor (5-HT2AR) contributes to the regulation of impulsive behavior and also mediates some of the behavioral effects of cocaine. We hypothesized that the selective 5-HT2AR antagonist M100907 would reduce inherent levels of impulsivity and attenuate impulsive responding induced by cocaine in two animal models of impulsivity, the differential reinforcement of low rate (DRL) task and the one-choice serial reaction time (1-CSRT) task. M100907 reduced rates of responding in the DRL task and premature responding in the 1-CSRT task. Conversely, cocaine disrupted rates of responding in the DRL task and increased premature responding in the 1-CSRT task. M100907 attenuated cocaine-induced increases in specific markers of behavioral disinhibition in the DRL and 1-CSRT tasks. These results suggest that the 5-HT2AR regulates inherent impulsivity, and that blockade of the 5-HT2AR alleviates specific aspects of elevated levels of impulsivity induced by cocaine exposure. These data point to the 5-HT 2AR as an important regulatory substrate in impulse control.",
keywords = "5-HT receptor, behavioral disinhibition, cocaine, differential reinforcement of low rate task, impulsivity, one-choice serial reaction time task, rat",
author = "Noelle Anastasio and Stoffel, {Erin C.} and Fox, {Robert G.} and Bubar, {Marcy J.} and Rice, {Kenner C.} and Moeller, {Frederick G.} and Kathryn Cunningham",
year = "2011",
month = "6",
doi = "10.1097/FBP.0b013e328345f90d",
language = "English (US)",
volume = "22",
pages = "248--261",
journal = "Behavioural Pharmacology",
issn = "0955-8810",
publisher = "Lippincott Williams and Wilkins",
number = "3",

}

TY - JOUR

T1 - Serotonin (5-hydroxytryptamine) 5-HT2A receptor

T2 - Association with inherent and cocaine-evoked behavioral disinhibition in rats

AU - Anastasio, Noelle

AU - Stoffel, Erin C.

AU - Fox, Robert G.

AU - Bubar, Marcy J.

AU - Rice, Kenner C.

AU - Moeller, Frederick G.

AU - Cunningham, Kathryn

PY - 2011/6

Y1 - 2011/6

N2 - Alterations in the balance of functional activity within the serotonin [5-hydroxytryptamine (5-HT)] system are hypothesized to underlie impulse control. Cocaine-dependent subjects consistently show greater impulsivity relative to nondrug using control subjects. Preclinical studies suggest that the 5-HT2A receptor (5-HT2AR) contributes to the regulation of impulsive behavior and also mediates some of the behavioral effects of cocaine. We hypothesized that the selective 5-HT2AR antagonist M100907 would reduce inherent levels of impulsivity and attenuate impulsive responding induced by cocaine in two animal models of impulsivity, the differential reinforcement of low rate (DRL) task and the one-choice serial reaction time (1-CSRT) task. M100907 reduced rates of responding in the DRL task and premature responding in the 1-CSRT task. Conversely, cocaine disrupted rates of responding in the DRL task and increased premature responding in the 1-CSRT task. M100907 attenuated cocaine-induced increases in specific markers of behavioral disinhibition in the DRL and 1-CSRT tasks. These results suggest that the 5-HT2AR regulates inherent impulsivity, and that blockade of the 5-HT2AR alleviates specific aspects of elevated levels of impulsivity induced by cocaine exposure. These data point to the 5-HT 2AR as an important regulatory substrate in impulse control.

AB - Alterations in the balance of functional activity within the serotonin [5-hydroxytryptamine (5-HT)] system are hypothesized to underlie impulse control. Cocaine-dependent subjects consistently show greater impulsivity relative to nondrug using control subjects. Preclinical studies suggest that the 5-HT2A receptor (5-HT2AR) contributes to the regulation of impulsive behavior and also mediates some of the behavioral effects of cocaine. We hypothesized that the selective 5-HT2AR antagonist M100907 would reduce inherent levels of impulsivity and attenuate impulsive responding induced by cocaine in two animal models of impulsivity, the differential reinforcement of low rate (DRL) task and the one-choice serial reaction time (1-CSRT) task. M100907 reduced rates of responding in the DRL task and premature responding in the 1-CSRT task. Conversely, cocaine disrupted rates of responding in the DRL task and increased premature responding in the 1-CSRT task. M100907 attenuated cocaine-induced increases in specific markers of behavioral disinhibition in the DRL and 1-CSRT tasks. These results suggest that the 5-HT2AR regulates inherent impulsivity, and that blockade of the 5-HT2AR alleviates specific aspects of elevated levels of impulsivity induced by cocaine exposure. These data point to the 5-HT 2AR as an important regulatory substrate in impulse control.

KW - 5-HT receptor

KW - behavioral disinhibition

KW - cocaine

KW - differential reinforcement of low rate task

KW - impulsivity

KW - one-choice serial reaction time task

KW - rat

UR - http://www.scopus.com/inward/record.url?scp=79955473049&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79955473049&partnerID=8YFLogxK

U2 - 10.1097/FBP.0b013e328345f90d

DO - 10.1097/FBP.0b013e328345f90d

M3 - Article

C2 - 21499079

AN - SCOPUS:79955473049

VL - 22

SP - 248

EP - 261

JO - Behavioural Pharmacology

JF - Behavioural Pharmacology

SN - 0955-8810

IS - 3

ER -