Regional elevations in microglial activation and cerebral glucose utilization in frontal white matter tracts of rhesus monkeys following prolonged cocaine self-administration

  • Hilary R. Smith
  • Thomas J. R. Beveridge
  • Susan H. Nader
  • Michael A. Nader
  • Linda J. PorrinoEmail author
Original Article


It has been shown that exposure to cocaine can result in neuroinflammatory responses. Microglia, the resident CNS immune cells, undergo a transition to an activated state when challenged. In rodents, and possibly humans, cocaine exposure activates microglia. The goal of this study was to assess the extent and magnitude of microglial activation in rhesus monkeys with an extensive history of cocaine self-administration. Male rhesus monkeys (N = 4/group) were trained to respond on a fixed-interval 3-min schedule of food or 0.3 mg/kg/injection cocaine presentation (30 reinforcers/session) for 300 sessions. At the end of the final session, monkeys were administered 2-[14C]deoxyglucose intravenously and 45 min later euthanized. Brain sections were used for autoradiographic assessments of glucose utilization and for microglia activation with [3H]PK11195, a marker for the microglial 18-kDa translocator protein. There were no group differences in gray matter [3H]PK11195 binding, while binding was significantly greater in cocaine self-administration animals as compared to food controls in 8 of the 11 white matter tracts measured at the striatal level. Binding did not differ from control at other levels. There were also significant increases in white matter local cerebral glucose utilization at the striatal level, which were positively correlated with [3H]PK11195 binding. The present findings demonstrate an elevation in [3H]PK11195 binding in forebrain white matter tracts of nonhuman primates with a prolonged history of cocaine self-administration. These elevations were also associated with greater cerebral metabolic rates. These data suggest that white matter deficits may contribute to behavioral, motivational, and cognitive impairments observed in cocaine abusers.


Cocaine Self-administration Microglia Neuroinflammation Rhesus monkey Local cerebral glucose utilization 



Funding for this study was provided by the National Institute of Drug Abuse Grant nos. DA09085 and DA06634. The authors wish to thank Tonya Calhoun for her excellent technical assistance.

Compliance with ethical standards

Conflict of interest

The authors declare they have no conflicts of interest.

Ethical approval

All applicable international, national, and institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution at which the studies were conducted.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Hilary R. Smith
    • 1
  • Thomas J. R. Beveridge
    • 1
    • 2
  • Susan H. Nader
    • 1
  • Michael A. Nader
    • 1
  • Linda J. Porrino
    • 1
    Email author
  1. 1.Department of Physiology and Pharmacology, Wake Forest School of MedicineCenter for the Neurobiology of Addiction Treatment, One Medical Center BoulevardWinston-SalemUSA
  2. 2.Medical Affairs-OncologyIpsen Biopharmaceuticals Inc.Basking RidgeUSA

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