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Brain Structure and Function

, Volume 221, Issue 3, pp 1681–1689 | Cite as

Optogenetic inhibition of cortical afferents in the nucleus accumbens simultaneously prevents cue-induced transient synaptic potentiation and cocaine-seeking behavior

  • Michael T. StefanikEmail author
  • Yonatan M. Kupchik
  • Peter W. Kalivas
Original Article

Abstract

Animal models of relapse reveal that the motivation to seek drug is regulated by enduring morphological and physiological changes in the nucleus accumbens, as well as transient synaptic potentiation in the accumbens core (NAcore) that parallels drug-seeking behavior. The current study sought to examine the link between the behavioral and synaptic consequences of cue-induced cocaine seeking by optically silencing glutamatergic afferents to the NAcore from the prelimbic cortex (PL). Adeno-associated virus coding for the inhibitory opsin archaerhodopsin was microinjected into PL, and optical fibers were targeted to NAcore. Animals were trained to self-administer cocaine followed by extinction training, and then underwent cue-induced reinstatement in the presence or absence of 15 min of optically induced inhibition of PL fibers in NAcore. Inhibiting the PL-to-NAcore projection blocked reinstated behavior and was paralleled by decreased dendritic spine head diameter and AMPA/NMDA ratio relative to sham-laser control rats. Interestingly, while spine density was elevated after extinction training, no further effects were observed by cued reinstatement or optical inhibition. These findings validate the critical role for PL afferents to the NAcore in simultaneously regulating both reinstated behavior and the associated transient synaptic potentiation.

Keywords

Optogenetic Nucleus accumbens Prelimbic prefrontal cortex Archaerhodopsin Dendritic spines Reinstatement Cocaine seeking 

Notes

Acknowledgments

This work was supported by National Institutes of Health T32 DA7288 and Grants DA015369, DA012513, and DA003906 (P.W.K.).

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Michael T. Stefanik
    • 1
    • 2
    Email author
  • Yonatan M. Kupchik
    • 1
    • 3
  • Peter W. Kalivas
    • 1
  1. 1.Department of NeuroscienceMedical University of South CarolinaCharlestonUSA
  2. 2.Department of NeuroscienceRosalind Franklin University of Medicine and ScienceNorth ChicagoUSA
  3. 3.Department of Medical NeurobiologyHebrew UniversityJerusalemIsrael

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