TY - JOUR
T1 - Orbitofrontal activation restores insight lost after cocaine use
AU - Lucantonio, Federica
AU - Takahashi, Yuji K.
AU - Hoffman, Alexander F.
AU - Chang, Chun Yun
AU - Bali-Chaudhary, Sheena
AU - Shaham, Yavin
AU - Lupica, Carl R.
AU - Schoenbaum, Geoffrey
N1 - Funding Information:
The authors would like to thank K. Deisseroth (Stanford University) and the Gene Therapy Center at the University of North Carolina at Chapel Hill core for providing viral reagents, and B. Harvey of the NIDA Optogenetic and Transgenic Core for technical advice on their use. This work was supported by funding from the National Institute on Drug Abuse (NIDA). The opinions expressed in this article are the authors’ own and do not reflect the view of the National Institutes of Health, the Department of Health and Human Services, or the United States government.
PY - 2014/8
Y1 - 2014/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84905101731&partnerID=8YFLogxK
U2 - 10.1038/nn.3763
DO - 10.1038/nn.3763
M3 - Article
C2 - 25042581
AN - SCOPUS:84905101731
SN - 1097-6256
VL - 17
SP - 1092
EP - 1099
JO - Nature neuroscience
JF - Nature neuroscience
IS - 8
ER -