期刊
CHANNELS
卷 6, 期 1, 页码 11-17出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/chan.19324
关键词
cocaine; dorsal striatum; VTA; GluA1; Ca(v)1.3; dopamine D2; ERK; CREB; DARPP-32; Akt; GSK3 beta
资金
- NIDA [K01 DA14057, R21 DA023686, DA007274-19]
- Austrian Science Fund [P20670]
- Deutsche Forschungsgemeinschaft
- Austrian Science Fund (FWF) [P20670] Funding Source: Austrian Science Fund (FWF)
- Austrian Science Fund (FWF) [P 20670] Funding Source: researchfish
AMPA receptor (AMPAR) plasticity at glutamatergic synapses in the mesostriatal dopaminergic pathway has been implicated in persistent cocaine-induced behavioral responses; however, the precise mechanism underlying these changes remains unknown. Utilizing cocaine psychomotor sensitization in mice we find that repeated cocaine results in a basal reduction of Ser 845 GluA1 and cell surface GluA1 levels in the dorsal striatum (dStr) following a protracted withdrawal period, an adaptation that is dependent on Ca(v)1.3 channels but not those expressed in the VTA. We find that the basally-induced decrease in this phosphoprotein is the result of recruitment of the striatal dopamine D2 pathway, as evidenced by enhanced levels of D2 receptor (D2R) mRNA expression and D2R function as examined using the D2R antagonist, eticlopride, as well as alterations in the phosphorylation status of several downstream molecular targets of D2R's, including CREB, DARPP-32, Akt and GSK3 beta. Taken together with our recently published findings examining similar phenomena in the nucleus accumbens (NAc), these results underscore the utilization of divergent molecular mechanisms in the dStr, in mediating cocaine-induced persistent behavioral changes.
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