TY - JOUR
T1 - Transient synaptic potentiation in nucleus accumbens shell during refraining from cocaine seeking
AU - Roberts-Wolfe, Douglas J.
AU - Heinsbroek, Jasper A.
AU - Spencer, Sade M.
AU - Bobadilla, Ana Clara
AU - Smith, Alexander C.W.
AU - Gipson, Cassandra D.
AU - Kalivas, Peter W.
N1 - Publisher Copyright:
© 2019 Society for the Study of Addiction
PY - 2020/5/1
Y1 - 2020/5/1
N2 - 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.
AB - 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.
KW - accumbens
KW - cocaine
KW - glutamate
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U2 - 10.1111/adb.12759
DO - 10.1111/adb.12759
M3 - Article
C2 - 31062493
AN - SCOPUS:85065436575
SN - 1355-6215
VL - 25
JO - Addiction Biology
JF - Addiction Biology
IS - 3
M1 - e12759
ER -