Differential cocaine-induced modulation of glutamate and dopamine transporters after contingent and non-contingent administration.
Although dopamine and glutamate transmission has been implicated in cocaine dependence, the effects of the extinction of cocaine self-administration on protein transporters in both of these neurotransmitter systems remain unknown. We have used a yoked-box procedure to simultaneously test rats in triads, one rat that actively self-administered cocaine (CONT), while the other two received yoked injections of either cocaine (NON-CONT) or saline (SALINE). The brains in each triad were removed and processed for quantitative autoradiography immediately after the last session of cocaine self-administration (Day 0), or after 1, 5, or 10 days of extinction, and excitatory amino acid transporters (EAATs) and dopamine transporter (DAT) binding was examined. When compared to NON-CONT and SALINE animals, binding of radioligand to EAATs was significantly lower in the hippocampal CA1 field and the cerebellar cortex of CONT rats on Day 0, although it was significantly higher after 1 day of extinction in the infralimbic cortex. No differences in EAAT binding were observed after 5 or 10 days of extinction in any of the brain regions analyzed. In contrast and at all the time points of extinction, binding to DAT was significantly enhanced in CONT animals when compared to SALINE and NON-CONT rats in different forebrain and mesencephalic regions, including the nucleus accumbens, ventral tegmental area or caudate putamen. These results suggest that changes in protein transporter binding after cocaine self-administration and extinction are transient for EAAT while they are more enduring for DAT, and that they depend on the type of access to cocaine.
Miguéns
Miguel
M
Departamento de Psicobiología, Universidad Nacional de Educación a Distancia, C/ Juan del Rosal n degrees 10, 28040 Madrid, Spain.
Crespo
José Antonio
JA
Del Olmo
Nuria
N
Higuera-Matas
Alejandro
A
Montoya
Gonzalo L
GL
García-Lecumberri
Carmen
C
Ambrosio
Emilio
E
D027322:Amino Acid Transport System X-AG / Q000378:metabolism*; D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology; D001345:Autoradiography; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology*; D008297:Male; D015999:Multivariate Analysis; D011485:Protein Binding / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D011917:Rats, Inbred Lew; D012054:Reinforcement, Psychology; D012646:Self Administration; D013997:Time Factors; D014316:Tritium / Q000378:metabolism
D027322:Amino Acid Transport System X-AG; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D014316:Tritium; D001224:Aspartic Acid; C021279:(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester; D003042:Cocaine