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, K. A. Cunningham

Research output: Contribution to journalArticlepeer-review

74 Scopus citations


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
Issue number2
StatePublished - Apr 2009


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

ASJC Scopus subject areas

  • Behavioral Neuroscience


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