title: Orbitofrontal activation restores insight lost after cocaine use.
abstract: Addiction is characterized by a lack of insight into the likely outcomes of one's behavior. Insight, or the ability to imagine outcomes, is evident when outcomes have not been directly experienced. Using this concept, work in both rats and humans has recently identified neural correlates of insight in the medial and orbital prefrontal cortices. We found that these correlates were selectively abolished in rats by cocaine self-administration. Their abolition was associated with behavioral deficits and reduced synaptic efficacy in orbitofrontal cortex, the reversal of which by optogenetic activation restored normal behavior. These results provide a link between cocaine use and problems with insight. Deficits in these functions are likely to be particularly important for problems such as drug relapse, in which behavior fails to account for likely adverse outcomes. As such, our data provide a neural target for therapeutic approaches to address these defining long-term effects of drug use.
authors.affiliation: 1] National Institute on Drug Abuse Intramural Research Program, Baltimore, Maryland, USA. [2] Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Federica
authors.initials: F
authors.lastname: Lucantonio
authors.affiliation: National Institute on Drug Abuse Intramural Research Program, Baltimore, Maryland, USA.
authors.forename: Yuji K
authors.initials: YK
authors.lastname: Takahashi
authors.affiliation: National Institute on Drug Abuse Intramural Research Program, Baltimore, Maryland, USA.
authors.forename: Alexander F
authors.initials: AF
authors.lastname: Hoffman
authors.affiliation: National Institute on Drug Abuse Intramural Research Program, Baltimore, Maryland, USA.
authors.forename: Chun Yun
authors.initials: CY
authors.lastname: Chang
authors.affiliation: National Institute on Drug Abuse Intramural Research Program, Baltimore, Maryland, USA.
authors.forename: Sheena
authors.initials: S
authors.lastname: Bali-Chaudhary
authors.affiliation: National Institute on Drug Abuse Intramural Research Program, Baltimore, Maryland, USA.
authors.forename: Yavin
authors.initials: Y
authors.lastname: Shaham
authors.affiliation: 1] National Institute on Drug Abuse Intramural Research Program, Baltimore, Maryland, USA. [2].
authors.forename: Carl R
authors.initials: CR
authors.lastname: Lupica
authors.affiliation: 1] National Institute on Drug Abuse Intramural Research Program, Baltimore, Maryland, USA. [2] Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland, USA. [3] Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University, Baltimore, Maryland, USA. [4].
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Schoenbaum
mesh_terms: D000818:Animals; D001364:Awareness / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects*; D003042:Cocaine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D007858:Learning / Q000187:drug effects*; D008297:Male; D062308:Optogenetics; D017397:Prefrontal Cortex / Q000166:cytology / Q000187:drug effects* / Q000503:physiopathology; D051381:Rats; D020318:Rats, Long-Evans; D012646:Self Administration; D013569:Synapses / Q000187:drug effects
chemical_list: D018765:Dopamine Uptake Inhibitors; D003042:Cocaine