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Functional connectivity in frontal-striatal brain networks and cocaine self-administration in female rhesus monkeys

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Abstract

Rationale

Cocaine addiction is characterized by alternating cycles of abstinence and relapse and loss of control of drug use despite severe negative life consequences associated with its abuse.

Objective

The objective of the present study was to elucidate critical neural circuits involved in individual vulnerabilities to resumption of cocaine self-administration following prolonged abstinence.

Methods

The subjects were three female rhesus monkeys in prolonged abstinence following a long history of cocaine self-administration. Initial experiments examined the effects of acute cocaine administration (0.3 mg/kg, IV) on functional brain connectivity across the whole brain and in specific brain networks related to behavioral control using functional magnetic resonance imaging in fully conscious subjects. Subsequently, these subjects were allowed to resume cocaine self-administration to determine whether loss of basal connectivity within specific brain networks predicted the magnitude of resumption of cocaine intake following prolonged abstinence.

Results

Acute cocaine administration robustly decreased global functional connectivity and selectively impaired top-down prefrontal circuits that control behavior, while sparing connectivity of striatal areas within limbic circuits. Importantly, impaired connectivity between prefrontal and striatal areas during abstinence predicted cocaine intake when these subjects were provided renewed access to cocaine.

Conclusions

Based on these findings, loss of prefrontal to striatal functional connectivity may be a critical mechanism underlying the negative downward spiral of cycles of abstinence and relapse that characterizes cocaine addiction.

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Acknowledgments

The authors would like to thank both Juliet Brown and Lisa Neidert for their expert technical assistance. These studies were supported by USPHS grants DA010344, DA034232, DA031246, and RR00165. They were furthermore supported by an award (UL1RR025008) from the Atlanta Clinical and Translational Science Institute and by the Office of Research Infrastructure Programs ODP51OD11132.

Conflict of interest

The authors declare no competing financial interests.

Author information

Authors and Affiliations

  1. Division of Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA

    K. S. Murnane, E. Maltbie & L. L. Howell

  2. Department of Radiology & Imaging Sciences, Emory University School of Medicine, Atlanta, GA, USA

    K. S. Gopinath

  3. Department of Physiology & Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC, USA

    J. B. Daunais

  4. School of Biomedical Engineering and Sciences, Virginia Tech-Wake Forest University, Winston-Salem, NC, USA

    Q. K. Telesford

  5. Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA

    L. L. Howell

  6. Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, Atlanta, GA, 30322, USA

    L. L. Howell

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  1. K. S. Murnane
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  3. E. Maltbie
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  4. J. B. Daunais
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  6. L. L. Howell
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Correspondence to L. L. Howell.

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Murnane, K.S., Gopinath, K.S., Maltbie, E. et al. Functional connectivity in frontal-striatal brain networks and cocaine self-administration in female rhesus monkeys. Psychopharmacology 232, 745–754 (2015). https://doi.org/10.1007/s00213-014-3709-9

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  • DOI: https://doi.org/10.1007/s00213-014-3709-9

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