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

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.

Cocaine-induced projection-specific and cell type-specific adaptations in the nucleus accumbens

“…Furthermore, in mice that undergo extinction training prior to re-exposure to cocaine-associated discrete cues, both NAcCo D1 and D2 MSNs show increased AMPAR/NMDAR ratio, suggesting that cue-induced relapse is effectively balanced by the relative activation patterns of these two neuronal populations 90 . This is partially supported by results from the rat NAcSh, wherein there is a transient increase in the AMPAR/NMDAR ratio during drug-refraining, presumably driven by D2 MSNs 91 . However, the same paper found no significant differences in the AMPAR/NMDAR ratio of D1 and D2 NAcSh MSNs in mice, although there was increased innervation of D2 MSNs relative to D1 91 .…”

“…This is partially supported by results from the rat NAcSh, wherein there is a transient increase in the AMPAR/NMDAR ratio during drug-refraining, presumably driven by D2 MSNs 91 . However, the same paper found no significant differences in the AMPAR/NMDAR ratio of D1 and D2 NAcSh MSNs in mice, although there was increased innervation of D2 MSNs relative to D1 91 . Thus, these results suggest that differential potentiation of NAcCo D1 and D2 MSN excitatory inputs in response to contextual or discrete cocaine-associated cues regulates the balance between cocaine seeking or refraining behaviors.…”

∆9-Tetrahydrocannabinol Self-Administration Induces Cell-Type Specific Adaptations and cFOS Expression in the Nucleus Accumbens Core

“…GABAergic D1-and D2-medium spiny neurons (MSNs) together comprise 90-95% of all neurons in the NAcore 29 , express the D1 or the D2 dopamine receptor respectively and have opposing roles in and reward behaviors [30][31][32][33][34] . Studies using cell type speci c expression of activity indicators such as cfos immunoreactivity or cell selective opto-or chemogenetic stimulation in the nucleus accumbens demonstrate that D1 MSNs promote and D2 MSNs inhibit reward behaviors 30,31 .…”