Opposite pre-and post-synaptic adaptations in the glutamatergic transmission in nucleus accumbens core, but not shell, underlies the long term sensitization to cocaine after a single restraint stress
García Keller, C*; Martínez, S*; Esparza, A.*; Cancela, L.M#.
IFEC CONICET, Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre esq. Medina Allende, Ciudad de Córdoba, CP: 5016.
Several evidences indicate that cocaine is able to induce behavioural and molecular sensitization in both, the dopaminergic (DA) and glutamatergic (Glu) mesocorticolimbic systems. The aim of this work was to study if the basal concentration of extracellular Glu as well as the AMPA receptor expression (AMPAR) participates in the long-term cross-sensitization between stress and cocaine. Wistar rats were restrained for two hours, while control animals were left undisturbed in their cages.Twenty-one days after this stress episode: I) Microdialysis: basal extracellular and saline- or cocaine (15 mg/kg ip) induced Glu levels were determinated by HPLC in NAc Core and Shell.II) AMPAR in Core after ip injection of saline or cocaine. Our results demonstrate that pre-stressed animals have raised basal extracellular concentrations of glutamate in the core, but not shell, and this could be related with the decrease in the cocaine-induced glutamate release in the core as compared with control values. We propose that the increase observed in the AMPAR in pre-stressed animals could be associated with the decrease in glutamate release after stimulus. These results are discussed in the context of disrupted glutamate homeostasis induced by acute stress 21 days before the cocaine challenge.
