Stimulation of 5-HT2C receptors attenuates cue and cocaine-primed reinstatement of cocaine-seeking behavior in rats

Janet Neisewander, Jazmin I. Acosta

Research output: Contribution to journalArticlepeer-review

77 Scopus citations


The extinction/reinstatement model has been used in this study to examine the role of 5-HT2C receptors in cocaine-seeking behavior elicited by cocaine-associated cues and cocaine-priming injections. Rats that had been trained to press a lever for cocaine (0.75 mg/kg/0.1 ml, intravenously) paired with light and tone cues underwent daily extinction sessions, during which responding had no consequences. After responding diminished, rats were tested for reinstatement of responding by either response-contingent presentations of the cues or a cocaine-priming injection (10 mg/kg, intraperitoneal, i.p.), with and without pretreatment with the 5-HT2C/2B receptor agonist, MK 212 (0.0-1.0 mg/kg, i.p.). MK 212 attenuated cue and cocaine-primed reinstatement, as well as spontaneous and cocaine-induced locomotion at all doses tested. These effects were reversed by coadministration of the 5-HT2C-selective receptor antagonist, SB 242 084 (3.0 mg/kg, i.p.), suggesting they are 5-HT2C receptor-mediated. Although we cannot rule out the possibility that motor impairment might have been involved in the MK 212 effects on cocaine-seeking behavior, some aspects of the data favor the explanation that MK 212 decreases the motivational effects of cocaine and cocaine cues. The latter interpretation is consistent with a growing body of literature suggesting that 5-HT2C receptors play a role in motivated behaviors in general.

Original languageEnglish (US)
Pages (from-to)791-800
Number of pages10
JournalBehavioural pharmacology
Issue number8
StatePublished - Dec 2007


  • 5-HT receptors
  • Conditioned reinforcement
  • Extinction
  • Incentive motivation
  • MK 212
  • Rat
  • SB 242 084

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health


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