title: Single exposure to cocaine impairs aspartate uptake in the pre-frontal cortex via dopamine D1-receptor dependent mechanisms.
abstract: Dopamine and glutamate play critical roles in the reinforcing effects of cocaine. We demonstrated that a single intraperitoneal administration of cocaine induces a significant decrease in [(3)H]-d-aspartate uptake in the pre-frontal cortex (PFC). This decrease is associated with elevated dopamine levels, and requires dopamine D1-receptor signaling (D1R) and adenylyl cyclase activation. The effect was observed within 10min of cocaine administration and lasted for up to 30min. This rapid response is related to D1R-mediated cAMP-mediated activation of PKA and phosphorylation of the excitatory amino acid transporters EAAT1, EAAT2 and EAAT3. We also demonstrated that cocaine exposure increases extracellular d-aspartate, l-glutamate and d-serine in the PFC. Our data suggest that cocaine activates dopamine D1 receptor signaling and PKA pathway to regulate EAATs function and extracellular EAA level in the PFC.
authors.affiliation: Laboratório de Neurofarmacologia, Departamento de Fisiologia e Farmacologia, Universidade Federal Fluminense, Niterói, Brazil. Electronic address: msathler@id.uff.br.
authors.forename: Matheus Figueiredo
authors.initials: MF
authors.lastname: Sathler
authors.affiliation: Laboratório de Neuroquímica, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil. Electronic address: stutz@biof.ufrj.br.
authors.forename: Bernardo
authors.initials: B
authors.lastname: Stutz
authors.affiliation: Laboratório de Neurofarmacologia, Departamento de Fisiologia e Farmacologia, Universidade Federal Fluminense, Niterói, Brazil. Electronic address: robertta.martins.cbio@gmail.com.
authors.forename: Robertta Silva
authors.initials: RS
authors.lastname: Martins
authors.affiliation: Laboratório de Neurofarmacologia, Departamento de Fisiologia e Farmacologia, Universidade Federal Fluminense, Niterói, Brazil; Laboratório de Neurofisiologia Molecular, Departamento de Fisiologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil. Electronic address: msp_biomed@yahoo.com.br.
authors.forename: Maurício
authors.initials: M
authors.lastname: Dos Santos Pereira
authors.affiliation: Laboratório de Neurofarmacologia, Departamento de Fisiologia e Farmacologia, Universidade Federal Fluminense, Niterói, Brazil. Electronic address: neyrp@bol.com.br.
authors.forename: Ney Roner
authors.initials: NR
authors.lastname: Pecinalli
authors.affiliation: Laboratório de Neuroquímica, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil. Electronic address: lsantos@biof.ufrj.br.
authors.forename: Luis E
authors.initials: LE
authors.lastname: Santos
authors.affiliation: Laboratório de Fisico-Química Biológica Aída Hassón-Voloch Instituto de Biofísica Carlos Chagas Filho Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil. Electronic address: rtsilva@biof.ufrj.br.
authors.forename: Rosilane
authors.initials: R
authors.lastname: Taveira-da-Silva
authors.affiliation: Laboratório de Fisico-Química Biológica Aída Hassón-Voloch Instituto de Biofísica Carlos Chagas Filho Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil. Electronic address: lowe@biof.ufrj.br.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lowe
authors.affiliation: Laboratório de Neurofarmacologia, Departamento de Fisiologia e Farmacologia, Universidade Federal Fluminense, Niterói, Brazil. Electronic address: isis.grigorio@yahoo.com.br.
authors.forename: Isis Grigorio
authors.initials: IG
authors.lastname: de Freitas
authors.affiliation: Laboratório de Neuroquímica, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil. Electronic address: ramreis@biof.ufrj.br.
authors.forename: Ricardo Augusto
authors.initials: RA
authors.lastname: de Melo Reis
authors.affiliation: Laboratório de Neurofisiologia, Departamento de Ciências Fisiológicas, Instituto de Biologia Roberto Alcantara Gomes, Centro Biomédico, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil. Electronic address: ac_manhaes@yahoo.com.br.
authors.forename: Alex C
authors.initials: AC
authors.lastname: Manhães
authors.affiliation: Laboratório de Neurofarmacologia, Departamento de Fisiologia e Farmacologia, Universidade Federal Fluminense, Niterói, Brazil. Electronic address: kubrusly@vm.uff.br.
authors.forename: Regina C C
authors.initials: RC
authors.lastname: Kubrusly
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism*; D003042:Cocaine / Q000008:administration & dosage*; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D027341:Excitatory Amino Acid Transporter 1 / Q000378:metabolism; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D050580:Excitatory Amino Acid Transporter 3 / Q000378:metabolism; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D018765:Dopamine Uptake Inhibitors; C583261:Drd1 protein, mouse; D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D050580:Excitatory Amino Acid Transporter 3; D017447:Receptors, Dopamine D1; C493399:Slc1a1 protein, mouse; C493396:Slc1a2 protein, mouse; C493393:Slc1a3 protein, mouse; D001224:Aspartic Acid; D018698:Glutamic Acid; D012694:Serine; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D000262:Adenylyl Cyclases; D003042:Cocaine; D004298:Dopamine
keywords: cocaine; dopamine; glutamate; prefrontal cortex; transporter