Stimulation of medial prefrontal cortex serotonin 2C (5-HT 2C) receptors attenuates cocaine-seeking behavior

Nathan S. Pentkowski, Felicia D. Duke, Suzanne M. Weber, Lara A. Pockros, Andrew P. Teer, Elizabeth C. Hamilton, Kenneth J. Thiel, Janet Neisewander

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

Serotonin 2C receptor (5-HT 2C R) agonists administered systemically attenuate both cocaine-primed and cue-elicited reinstatement of extinguished cocaine-seeking behavior. To further elucidate the function of these receptors in addiction-like processes, this study examined the effects of microinfusing the 5-HT 2C R agonist MK212 (0, 10, 30, 100 ng/side/0.2 l) into the medial prefrontal cortex (mPFC) on cocaine self-administration and reinstatement of extinguished cocaine-seeking behavior. Male Sprague-Dawley rats were trained to self-administer cocaine (0.75 mg/kg, i.v.) paired with light and tone cues. Once responding stabilized, rats received MK212 microinfusions before tests for maintenance of cocaine self-administration. Next, extinction training to reduce cocaine-seeking behavior, defined as responses performed without cocaine reinforcement available, occurred until low extinction baselines were achieved. Rats then received MK212 microinfusions before tests for reinstatement of extinguished cocaine-seeking behavior elicited by cocaine-priming injections (10 mg/kg, i.p.) or response-contingent presentations of the cocaine-associated cues; operant responses during cocaine-primed reinstatement tests produced no consequences. MK212 microinfusions into the prelimbic and infralimbic, but not anterior cingulate, regions of the mPFC dose-dependently attenuated both cocaine-primed and cue-elicited reinstatement of extinguished cocaine-seeking behavior, but did not reliably affect cocaine self-administration. A subsequent experiment showed that the effects of MK212 (100 ng/side/0.2 l) on reinstatement of extinguished cocaine-seeking behavior were blocked by co-administration of the 5-HT 2C R antagonist SB242084 (200 ng/side/0.2 l). MK212 administered alone into the mPFC as a drug prime produced no discernable effects on cocaine-seeking behavior. These findings suggest that stimulation of 5-HT 2C Rs in the mPFC attenuates the incentive motivational effects produced by sampling cocaine or exposure to drug-paired cues.

Original languageEnglish (US)
Pages (from-to)2037-2048
Number of pages12
JournalNeuropsychopharmacology
Volume35
Issue number10
DOIs
Publication statusPublished - Sep 2010

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Keywords

  • addiction
  • craving
  • motivation
  • reinstatement
  • relapse
  • serotonin

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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