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Psychopharmacology

, Volume 236, Issue 1, pp 479–490 | Cite as

Attenuation of cocaine seeking in rats via enhancement of infralimbic cortical activity using stable step-function opsins

  • Victória A. Müller EwaldEmail author
  • Benjamin J. De Corte
  • Subhash C. Gupta
  • Katherine V. Lillis
  • Nandakumar S. Narayanan
  • John A. Wemmie
  • Ryan T. LaLumiere
Original Investigation
  • 219 Downloads

Abstract

Rationale

The infralimbic cortex (IL) and its downstream projection target the nucleus accumbens shell (NAshell) mediate the active suppression of cocaine-seeking behavior. Although an optogenetic approach would be beneficial for stimulating the IL and its efferents to study their role during reinstatement of cocaine seeking, the use of channelrhodopsin introduces significant difficulties, as optimal stimulation parameters are not known.

Objectives

The present experiments utilized a stable step-function opsin (SSFO) to potentiate endogenous activity in the IL and in IL terminals in the NAshell during cocaine-seeking tests to determine how these manipulations affect cocaine-seeking behaviors.

Methods

Rats first underwent 6-h access cocaine self-administration followed by 21–27 days in the homecage. Rats then underwent cue-induced and cocaine-primed drug-seeking tests during which the optogenetic manipulation was given. The same rats then underwent extinction training, followed by cue-induced and cocaine-primed reinstatements.

Results

Potentiation of endogenous IL activity did not significantly alter cue-induced or cocaine-primed drug seeking following the homecage period. However, following extinction training, enhancement of endogenous IL activity attenuated cue-induced reinstatement by 35% and cocaine-primed reinstatement by 53%. Stimulation of IL terminals in the NAshell did not consistently alter cocaine-seeking behavior.

Conclusion

These results suggest the utility of an SSFO-based approach for enhancing activity in a structure without driving specific patterns of neuronal firing. However, the utility of an SSFO-based approach for axon terminal stimulation remains unclear. Moreover, these results suggest that the ability of the IL to reduce cocaine seeking depends, at least in part, on rats first having undergone extinction training.

Keywords

Optogenetics Channelrhodopsin Reinstatement Incubation of craving Cocaine seeking 

Notes

Funding

R.T.L was supported by National Institute of Health R01 DA034684. J.A.W. was supported by the Department of Veterans Affairs (Merit Award), National Institute on Drug Abuse R01 DA037216, National Heart, Lung and Blood Institute R01 HL113863, and the Carver Foundation. N.S.N. was supported by National Institute of Health R01 NS089470.

Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflict of interest.

Supplementary material

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Victória A. Müller Ewald
    • 1
    • 2
    Email author
  • Benjamin J. De Corte
    • 1
    • 3
  • Subhash C. Gupta
    • 4
  • Katherine V. Lillis
    • 2
  • Nandakumar S. Narayanan
    • 1
    • 3
    • 5
  • John A. Wemmie
    • 1
    • 4
    • 5
  • Ryan T. LaLumiere
    • 1
    • 2
    • 5
  1. 1.Interdisciplinary Neuroscience ProgramUniversity of IowaIowa CityUSA
  2. 2.W311 Seashore Hall, Department of Psychological and Brain SciencesUniversity of IowaIowa CityUSA
  3. 3.Department of NeurologyUniversity of IowaIowa CityUSA
  4. 4.Department of PsychiatryUniversity of IowaIowa CityUSA
  5. 5.Iowa Neuroscience InstituteUniversity of IowaIowa CityUSA

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