title: Cav 1.3 L-type Ca ( 2+) channels mediate long-term adaptation in dopamine D2L-mediated GluA1 trafficking in the dorsal striatum following cocaine exposure.
abstract: 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 Cav 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 GSK3β. 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.
authors.affiliation: Graduate Program in Neuroscience, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Schierberl
authors.forename: Thomas
authors.initials: T
authors.lastname: Giordano
authors.forename: Shirish
authors.initials: S
authors.lastname: Satpute
authors.forename: Jin
authors.initials: J
authors.lastname: Hao
authors.forename: Gagandeep
authors.initials: G
authors.lastname: Kaur
authors.forename: Franz
authors.initials: F
authors.lastname: Hofmann
authors.forename: Sven
authors.initials: S
authors.lastname: Moosmang
authors.forename: Joerg
authors.initials: J
authors.lastname: Striessnig
authors.forename: Anjali
authors.initials: A
authors.lastname: Rajadhyaksha
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D020746:Calcium Channels, L-Type / Q000502:physiology*; D003042:Cocaine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D055785:Gene Knockdown Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D018091:Receptors, AMPA / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology
chemical_list: D020746:Calcium Channels, L-Type; D003042:Cocaine; D018765:Dopamine Uptake Inhibitors; D019950:Mitogen-Activated Protein Kinase 1; D012333:RNA, Messenger; D018091:Receptors, AMPA; D017448:Receptors, Dopamine D2; C485995:Cacna1d protein, mouse; C113776:dopamine D2L receptor; C104722:glutamate receptor ionotropic, AMPA 2