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 Gipson-Reichardt, 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
DOIs
StatePublished - Jan 1 2019
Externally publishedYes

Fingerprint

Neuronal Plasticity
Nucleus Accumbens
Cocaine
Neurons
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
N-Methyl-D-Aspartate Receptors
Pharmaceutical Preparations
Cues
AMPA Receptors
Electrophysiology
Glutamate Receptors
Metalloproteases
N-Methylaspartate
Dendrites
Reward
Transgenic Mice
Rodentia
Spine
Psychological Extinction

Keywords

  • accumbens
  • cocaine
  • glutamate

ASJC Scopus subject areas

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

Cite this

Roberts-Wolfe, D. J., Heinsbroek, J. A., Spencer, S. M., Bobadilla, A. C., Smith, A. C. W., Gipson-Reichardt, C., & Kalivas, P. W. (2019). Transient synaptic potentiation in nucleus accumbens shell during refraining from cocaine seeking. Addiction Biology, [e12759]. https://doi.org/10.1111/adb.12759

Transient synaptic potentiation in nucleus accumbens shell during refraining from cocaine seeking. / Roberts-Wolfe, Douglas J.; Heinsbroek, Jasper A.; Spencer, Sade M.; Bobadilla, Ana Clara; Smith, Alexander C.W.; Gipson-Reichardt, Cassandra; Kalivas, Peter W.

In: Addiction Biology, 01.01.2019.

Research output: Contribution to journalArticle

Roberts-Wolfe, Douglas J. ; Heinsbroek, Jasper A. ; Spencer, Sade M. ; Bobadilla, Ana Clara ; Smith, Alexander C.W. ; Gipson-Reichardt, Cassandra ; Kalivas, Peter W. / Transient synaptic potentiation in nucleus accumbens shell during refraining from cocaine seeking. In: Addiction Biology. 2019.
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