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Front Pharmacol. 2014 Oct 27;5:228. doi: 10.3389/fphar.2014.00228. eCollection 2014.

Adolescent cocaine exposure simplifies orbitofrontal cortical dendritic arbors.

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Department of Pediatrics, Emory University School of Medicine , Atlanta, GA, USA ; Yerkes National Primate Research Center, Emory University , Atlanta, GA, USA ; Graduate Program in Neuroscience, Emory University , Atlanta, GA, USA.
Graduate Program in Molecular and Systems Pharmacology, Emory University , Atlanta, GA, USA.
Department of Molecular Biophysics and Biochemistry, Yale University , New Haven, CT, USA ; Interdepartmental Neuroscience Program, Yale University , New Haven, CT, USA ; Department of Neurobiology, Yale University School of Medicine , New Haven, CT, USA.


Cocaine and amphetamine remodel dendritic spines within discrete cortico-limbic brain structures including the orbitofrontal cortex (oPFC). Whether dendrite structure is similarly affected, and whether pre-existing cellular characteristics influence behavioral vulnerabilities to drugs of abuse, remain unclear. Animal models provide an ideal venue to address these issues because neurobehavioral phenotypes can be defined both before, and following, drug exposure. We exposed mice to cocaine from postnatal days 31-35, corresponding to early adolescence, using a dosing protocol that causes impairments in an instrumental reversal task in adulthood. We then imaged and reconstructed excitatory neurons in deep-layer oPFC. Prior cocaine exposure shortened and simplified arbors, particularly in the basal region. Next, we imaged and reconstructed orbital neurons in a developmental-genetic model of cocaine vulnerability-the p190rhogap+/- mouse. p190RhoGAP is an actin cytoskeleton regulatory protein that stabilizes dendrites and dendritic spines, and p190rhogap+/- mice develop rapid and robust locomotor activation in response to cocaine. Despite this, oPFC dendritic arbors were intact in drug-naïve p190rhogap+/- mice. Together, these findings provide evidence that adolescent cocaine exposure has long-term effects on dendrite structure in the oPFC, and they suggest that cocaine-induced modifications in dendrite structure may contribute to the behavioral effects of cocaine more so than pre-existing structural abnormalities in this cell population.


addiction; adolescence; orbital; psychostimulant; sholl

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