Transient synaptic potentiation in nucleus accumbens shell during refraining from cocaine seeking

Douglas J. Roberts-Wolfe, Jasper A. Heinsbroek, Sade M. Spencer, Ana Clara Bobadilla, Alexander C.W. Smith, Cassandra D. Gipson, Peter W. Kalivas

Research output: Contribution to journalArticle

Abstract

Repeated exposure to drug-associated cues without reward (extinction) leads to refraining from drug seeking in rodents. We determined if refraining is associated with transient synaptic plasticity (t-SP) in nucleus accumbens shell (NAshell), akin to the t-SP measured in the NAcore during cue-induced reinstatement of drug seeking. Using whole cell patch electrophysiology, we found that medium spiny neurons (MSNs) in NAshell expressed increased ratio of AMPA to NMDA glutamate receptor currents during refraining, which normalized to baseline levels by the end of the 2-hour extinction session. Unlike t-SP observed in NAcore during reinstated drug seeking, neither dendrite spine head enlargement nor activation of matrix metalloproteases (MMP2/9) accompanied the increased AMPA:NMDA in NAshell during refraining. Refraining was also not associated with changes in paired pulse ratio, NMDA receptor current decay time, or AMPA receptor rectification index in NAshell MSNs. Our preliminary data in transgenic mice suggest that t-SP may increase D2-MSN inputs relative to D1-MSN inputs.

Original languageEnglish (US)
Article numbere12759
JournalAddiction Biology
Volume25
Issue number3
DOIs
StatePublished - May 1 2020

Keywords

  • accumbens
  • cocaine
  • glutamate

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology
  • Psychiatry and Mental health

Fingerprint Dive into the research topics of 'Transient synaptic potentiation in nucleus accumbens shell during refraining from cocaine seeking'. Together they form a unique fingerprint.

  • Cite this

    Roberts-Wolfe, D. J., Heinsbroek, J. A., Spencer, S. M., Bobadilla, A. C., Smith, A. C. W., Gipson, C. D., & Kalivas, P. W. (2020). Transient synaptic potentiation in nucleus accumbens shell during refraining from cocaine seeking. Addiction Biology, 25(3), [e12759]. https://doi.org/10.1111/adb.12759