D1, but not D2, receptor blockade within the infralimbic and medial orbitofrontal cortex impairs cocaine seeking in a region-specific manner

Addict Biol. 2018 Jan;23(1):16-27. doi: 10.1111/adb.12442. Epub 2016 Aug 31.


Evidence suggests that the infralimbic cortex (IL), a subregion of the ventromedial prefrontal cortex (vmPFC), suppresses cocaine-seeking behavior in a self-administration paradigm, whereas the more anterior vmPFC subregion, the medial orbitofrontal cortex (mOFC), has received very little attention in this regard. Despite the established dopaminergic innervation of the vmPFC, whether dopamine receptor blockade in each subregion alters the reinstatement of cocaine seeking is unclear. To address this issue, male Sprague-Dawley rats underwent 2 weeks of cocaine self-administration, followed by extinction training and reinstatement testing. Immediately prior to each reinstatement test, rats received microinjections of the D1 receptor antagonist SCH 23390, the D2 receptor antagonist sulpiride or their respective vehicles. D1 receptor blockade in the IL reduced cued reinstatement but had no effect on cocaine prime and cue + cocaine-prime reinstatement, whereas D2 receptor blockade in the IL had no effect on reinstatement. For the mOFC, however, D1 receptor blockade reduced cocaine seeking in all reinstatement types, whereas blocking D2 receptors in the mOFC had no effect on any form of cocaine seeking. These findings suggest different roles for D1 receptors in the IL versus the mOFC in regulating cocaine-seeking behavior. Moreover, even as previous work indicates that IL inactivation does not affect reinstatement but, rather, induces cocaine seeking during extinction, the present findings suggest that dopamine receptor activation in the IL is necessary for cocaine seeking under some circumstances.

Keywords: SCH 23390; cocaine prime; rat; self-administration; sulpiride; ventromedial prefrontal cortex.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Benzazepines / pharmacology*
  • Cocaine / administration & dosage*
  • Conditioning, Operant
  • Cues
  • Dopamine Antagonists / pharmacology*
  • Dopamine D2 Receptor Antagonists / pharmacology
  • Dopamine Uptake Inhibitors / administration & dosage*
  • Drug-Seeking Behavior / drug effects*
  • Extinction, Psychological
  • Male
  • Prefrontal Cortex / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D1 / antagonists & inhibitors
  • Receptors, Dopamine D2
  • Self Administration
  • Sulpiride / pharmacology*


  • Benzazepines
  • DRD2 protein, rat
  • Dopamine Antagonists
  • Dopamine D2 Receptor Antagonists
  • Dopamine Uptake Inhibitors
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • SCH 23390
  • Sulpiride
  • Cocaine