About this item:

202 Views | 462 Downloads

Author Notes:

Contact: Shannon L. Gourley, PhD, Yerkes National Primate Research Center, Emory University, 954 Gatewood Rd. NE, Atlanta GA 30329, 404-727-2482, shannon.l.gourley@emory.edu.

The authors thank Dr. Anthony Koleske, Ms. Kelsey Zimmermann, Mr. Andrew Swanson, and Ms. Elizabeth Pitts for valuable comments on this manuscript and Dr. Marina Wheeler for contributions to an early version of this document.

The authors have no conflicts to disclose.

Subjects:

Research Funding:

This work was supported by the Emory University Research Council, DA 034808, and DA 036737.

The Yerkes National Primate Research Center is supported by the Office of Research Infrastructure Programs/OD P51OD11132.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Cell Biology
  • adolescence
  • cingulate
  • D-amphetamine
  • dependence
  • drug abuse
  • impulsivity
  • infralimbic
  • orbitofrontal
  • prelimbic
  • review
  • MESSENGER-RNA EXPRESSION
  • COCAINE-SEEKING BEHAVIOR
  • CONDITIONED PLACE PREFERENCE
  • DENDRITIC SPINE DENSITY
  • INDUCED STRUCTURAL PLASTICITY
  • CONTEXT-INDUCED REINSTATEMENT
  • LATERAL ORBITOFRONTAL CORTEX
  • REVERSAL-LEARNING DEFICITS
  • CUE-INDUCED REINSTATEMENT
  • DOPAMINE D2 RECEPTORS

Synaptic Cytoskeletal Plasticity in the Prefrontal Cortex Following Psychostimulant Exposure

Tools:

Journal Title:

Traffic

Volume:

Volume 16, Number 9

Publisher:

, Pages 919-940

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Exposure to cocaine and amphetamine structurally reorganizes excitatory neurons in the medial and orbital prefrontal cortices (mPFC and oPFC), inducing dendritic spine proliferation in the mPFC and eliminating spines in the oPFC. Modifications may be causally associated with addiction etiology. Certain cytoskeletal regulatory proteins expressed in the oPFC and implicated in postnatal neural development also regulate behavioral sensitivity to cocaine, potentially opening a window of opportunity for the identification of novel pharmacotherapeutic targets in the treatment of drug abuse disorders. Addiction is characterized by maladaptive decision-making, a loss of control over drug consumption and habit-like drug seeking despite adverse consequences. These cognitive changes may reflect the effects of drugs of abuse on prefrontal cortical neurobiology. Here, we review evidence that amphetamine and cocaine fundamentally remodel the structure of excitatory neurons in the prefrontal cortex. We summarize evidence in particular that these psychostimulants have opposing effects in the medial and orbital prefrontal cortices ('mPFC' and 'oPFC', respectively). For example, amphetamine and cocaine increase dendrite length and spine density in the mPFC, while dendrites are impoverished and dendritic spines are eliminated in the oPFC. We will discuss evidence that certain cytoskeletal regulatory proteins expressed in the oPFC and implicated in postnatal (adolescent) neural development also regulate behavioral sensitivity to cocaine. These findings potentially open a window of opportunity for the identification of novel pharmacotherapeutic targets in the treatment of drug abuse disorders in adults, as well as in drug-vulnerable adolescent populations. Finally, we will discuss the behavioral implications of drug-related dendritic spine elimination in the oPFC, with regard to reversal learning tasks and tasks that assess the development of reward-seeking habits, both used to model aspects of addiction in rodents.

Copyright information:

© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Export to EndNote