.png){kind=icon}
.png){kind=icon}
Return
Stress-responsive nucleus accumbens dopamine D2 receptor-expressing neurons modulate cocaine-induced behavioral sensitization
.png){kind=icon}
OA
AI
B
B
M
Y
E
J
J
DOI：10.3389/fncel.2026.1919290.png)
.png){kind=icon}
Original request for help.png){kind=icon}
Share.png){kind=icon}
Save
Abstract
En 中文
Although both stress and cocaine induce robust plasticity within the nucleus accumbens core (NAcc); how these distinct experiences interact at the cellular level to shape behavior remains unclear. Here; we investigated the role of NAcc dopamine D2 receptor-expressing medium spiny neurons (D2R-MSNs) in integrating stress- and drug-induced signals. D2R-MSNs showed distinct activity responses; with increased activity during restraint stress and reduced activity following repeated cocaine exposure. Using the Cre-dependent Robust Activity Marking (cRAM) system; we found that cocaine exposure suppressed the activity of the subpopulation of D2R-MSNs previously recruited by stress. Optogenetic reactivation of these stress-tagged D2R-MSNs during withdrawal attenuated the expression of cocaine-induced behavioral sensitization. Transcriptomic profiling of stress-responsive D2R-MSNs identified cholecystokinin (Cck) as a candidate associated with this neuronal manipulation. Subsequent experiments showed that cocaine exposure increased CCK expression in NAcc D2R-MSNs; whereas conditional Cck knockdown reduced the expression of behavioral sensitization. Together; these findings suggest that stress-responsive D2R-MSNs contribute to the regulation of cocaine-induced behavioral sensitization and that CCK signaling within NAcc D2R-MSNs may be involved in this process.
Keywords:
stress
nucleus accumbens
optogenetics
cocaine
dopamine D2 receptor
activity-dependent labeling system
Journal
IF:
4
Papers:
6.4K
Citations:
2.3W
Organization
Cited Papers