Blockade of the Serotonin 5-HT 2A Receptor Suppresses Cue-Evoked Reinstatement of Cocaine-Seeking Behavior in a Rat Self-Administration Model

B. Á Nic Dhonnchadha, R. G. Fox, S. J. Stutz, K. C. Rice, Kathryn Cunningham

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

The serotonin 5-HT 2A receptor (5-HT 2AR) may play a role in reinstatement of drug-seeking. This study investigated the ability of a selective 5-HT 2AR antagonist to suppress reinstatement evoked by exposure to cues conditioned to cocaine self-administration. Cocaine self-administration (0.75 mg/kg/0.1 mL/6 s infusion; FR 4) was trained in naïve, free-fed rats to allow interpretation of results independent from changes related to food deprivation stress. Pretreatment with the selective 5-HT 2AR antagonist M100907 (volinanserin) failed to reduce rates of operant responding for cocaine infusions. On the other hand, M100907 (0.001-0.8 mg/kg ip) significantly suppressed the cue-induced reinstatement of cocaine-seeking behavior following extinction; effective M100907 doses did not alter operant responding for cues previously associated with sucrose self-administration. Importantly, a greater magnitude of active lever presses on the initial extinction session (high extinction responders) predicted the maximal susceptibility to M100907-induced suppression of cue-evoked reinstatement. The findings indicate that blockade of the 5-HT 2AR attenuates the incentive-motivational effects of cocaine-paired cues, particularly in high extinction responders, and suggests that M100907 may afford a therapeutic advance in suppression of cue-evoked craving and/or relapse.

Original languageEnglish (US)
Pages (from-to)382-396
Number of pages15
JournalBehavioral Neuroscience
Volume123
Issue number2
DOIs
StatePublished - Apr 2009

Fingerprint

Receptor, Serotonin, 5-HT2A
Self Administration
Cocaine
Cues
Serotonin
Food Deprivation
Aptitude
Sucrose
Motivation
MDL 100907
Recurrence
Psychological Extinction
Pharmaceutical Preparations

Keywords

  • 5-HT R antagonist
  • cocaine self-administration
  • cue-induced reinstatement
  • extinction
  • M100907

ASJC Scopus subject areas

  • Behavioral Neuroscience

Cite this

Blockade of the Serotonin 5-HT 2A Receptor Suppresses Cue-Evoked Reinstatement of Cocaine-Seeking Behavior in a Rat Self-Administration Model. / Dhonnchadha, B. Á Nic; Fox, R. G.; Stutz, S. J.; Rice, K. C.; Cunningham, Kathryn.

In: Behavioral Neuroscience, Vol. 123, No. 2, 04.2009, p. 382-396.

Research output: Contribution to journalArticle

@article{216bc860ef6340868c5de5cedb2a6609,
title = "Blockade of the Serotonin 5-HT 2A Receptor Suppresses Cue-Evoked Reinstatement of Cocaine-Seeking Behavior in a Rat Self-Administration Model",
abstract = "The serotonin 5-HT 2A receptor (5-HT 2AR) may play a role in reinstatement of drug-seeking. This study investigated the ability of a selective 5-HT 2AR antagonist to suppress reinstatement evoked by exposure to cues conditioned to cocaine self-administration. Cocaine self-administration (0.75 mg/kg/0.1 mL/6 s infusion; FR 4) was trained in na{\"i}ve, free-fed rats to allow interpretation of results independent from changes related to food deprivation stress. Pretreatment with the selective 5-HT 2AR antagonist M100907 (volinanserin) failed to reduce rates of operant responding for cocaine infusions. On the other hand, M100907 (0.001-0.8 mg/kg ip) significantly suppressed the cue-induced reinstatement of cocaine-seeking behavior following extinction; effective M100907 doses did not alter operant responding for cues previously associated with sucrose self-administration. Importantly, a greater magnitude of active lever presses on the initial extinction session (high extinction responders) predicted the maximal susceptibility to M100907-induced suppression of cue-evoked reinstatement. The findings indicate that blockade of the 5-HT 2AR attenuates the incentive-motivational effects of cocaine-paired cues, particularly in high extinction responders, and suggests that M100907 may afford a therapeutic advance in suppression of cue-evoked craving and/or relapse.",
keywords = "5-HT R antagonist, cocaine self-administration, cue-induced reinstatement, extinction, M100907",
author = "Dhonnchadha, {B. {\'A} Nic} and Fox, {R. G.} and Stutz, {S. J.} and Rice, {K. C.} and Kathryn Cunningham",
year = "2009",
month = "4",
doi = "10.1037/a0014592",
language = "English (US)",
volume = "123",
pages = "382--396",
journal = "Behavioral Neuroscience",
issn = "0735-7044",
publisher = "American Psychological Association Inc.",
number = "2",

}

TY - JOUR

T1 - Blockade of the Serotonin 5-HT 2A Receptor Suppresses Cue-Evoked Reinstatement of Cocaine-Seeking Behavior in a Rat Self-Administration Model

AU - Dhonnchadha, B. Á Nic

AU - Fox, R. G.

AU - Stutz, S. J.

AU - Rice, K. C.

AU - Cunningham, Kathryn

PY - 2009/4

Y1 - 2009/4

N2 - The serotonin 5-HT 2A receptor (5-HT 2AR) may play a role in reinstatement of drug-seeking. This study investigated the ability of a selective 5-HT 2AR antagonist to suppress reinstatement evoked by exposure to cues conditioned to cocaine self-administration. Cocaine self-administration (0.75 mg/kg/0.1 mL/6 s infusion; FR 4) was trained in naïve, free-fed rats to allow interpretation of results independent from changes related to food deprivation stress. Pretreatment with the selective 5-HT 2AR antagonist M100907 (volinanserin) failed to reduce rates of operant responding for cocaine infusions. On the other hand, M100907 (0.001-0.8 mg/kg ip) significantly suppressed the cue-induced reinstatement of cocaine-seeking behavior following extinction; effective M100907 doses did not alter operant responding for cues previously associated with sucrose self-administration. Importantly, a greater magnitude of active lever presses on the initial extinction session (high extinction responders) predicted the maximal susceptibility to M100907-induced suppression of cue-evoked reinstatement. The findings indicate that blockade of the 5-HT 2AR attenuates the incentive-motivational effects of cocaine-paired cues, particularly in high extinction responders, and suggests that M100907 may afford a therapeutic advance in suppression of cue-evoked craving and/or relapse.

AB - The serotonin 5-HT 2A receptor (5-HT 2AR) may play a role in reinstatement of drug-seeking. This study investigated the ability of a selective 5-HT 2AR antagonist to suppress reinstatement evoked by exposure to cues conditioned to cocaine self-administration. Cocaine self-administration (0.75 mg/kg/0.1 mL/6 s infusion; FR 4) was trained in naïve, free-fed rats to allow interpretation of results independent from changes related to food deprivation stress. Pretreatment with the selective 5-HT 2AR antagonist M100907 (volinanserin) failed to reduce rates of operant responding for cocaine infusions. On the other hand, M100907 (0.001-0.8 mg/kg ip) significantly suppressed the cue-induced reinstatement of cocaine-seeking behavior following extinction; effective M100907 doses did not alter operant responding for cues previously associated with sucrose self-administration. Importantly, a greater magnitude of active lever presses on the initial extinction session (high extinction responders) predicted the maximal susceptibility to M100907-induced suppression of cue-evoked reinstatement. The findings indicate that blockade of the 5-HT 2AR attenuates the incentive-motivational effects of cocaine-paired cues, particularly in high extinction responders, and suggests that M100907 may afford a therapeutic advance in suppression of cue-evoked craving and/or relapse.

KW - 5-HT R antagonist

KW - cocaine self-administration

KW - cue-induced reinstatement

KW - extinction

KW - M100907

UR - http://www.scopus.com/inward/record.url?scp=65349124145&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=65349124145&partnerID=8YFLogxK

U2 - 10.1037/a0014592

DO - 10.1037/a0014592

M3 - Article

VL - 123

SP - 382

EP - 396

JO - Behavioral Neuroscience

JF - Behavioral Neuroscience

SN - 0735-7044

IS - 2

ER -