Down-regulated GLT-1 expression in astrocytes are related to altered glutamate homeostasis in Nucleus Accumbens Core induced by stress

GARCIA KELLER, C; ESPARZA, M.A; MONGI BRAGATO, B; KALIVAS P.W; CANCELA, L.M.

Cancun

Congreso; ISN-ASN; 2013

DOWN-REGULATED GLT-1 EXPRESSION IN ASTROCYTES ARE RELATED TO ALTERED GLUTAMATE HOMEOSTASIS IN NUCLEUS ACCUMBENS CORE INDUCED BY RESTRAINT STRESS   García Keller, C*; Esparza, A.*; Mongi Bragato, B*; Kalivas, PW+; 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. cgarciakeller@fcq.unc.edu.ar +Department of Neurosciences, MUSC, Charleston, South Carolina.   Sensitization is associated with neuroplasticity in the dopaminergic (DA) and glutamatergic (Glu) mesocorticolimbic systems. It is well known that withdrawal (2-3 weeks) from chronic cocaine, disrupted glutamate homeostasis and decreased glutamate transporter-1 (GLT-1) expression in the nucleus accumbens (NAc) core; and that these changes were restored with ceftriaxone treatment. The aim of our study was to evaluate if stress-induced alterations in glutamate homeostasis and GLT-1, and if these changes can be restored with ceftriaxone pre-treatment. Male Wistar rats (250-350 g) were restrained for two hours, while control animals were left undisturbed in their cages. Twenty-one days after this single stress episode, the stress and non-stress groups were assigned to one of the following experiments: I) Microdialysis: basal Glu release was measured by HPLC in NAc Core and Shell by no-net-flux technique II) Western blot: 45 min later i.p. injection of saline or cocaine (15 mg/kg) animals were sacrificed for GLT-1 expression in NAc Core. Another group of non-stress and stress animals were randomly divided in two groups since day 16 following the stress episode and received five daily injections of vehicle or ceftriaxone (200 mg/kg). Twenty-four hours later the last injection were assigned to the following experiments: I) Locomotor activity was registered in response to saline or cocaine (15 mg/kg i.p.) for 45 min and then sacrificed for II) Western blot: 45 min later i.p. injection of saline or cocaine (15 mg/kg) animals were sacrificed for GLT-1 expression in NAc Core. Our results demonstrate that pre-stressed animals showed increased basal levels of Glu in Core, but not shell, and that this could be related to a decreased expression of GLT-1 in NAc. Interestingtly, the expression of stress-induced behavioral sensitization was abrogated when animals were treated with ceftriaxone five days before cocaine challenge. We speculate that ceftriaxone might restore glutamate homeostasis in pre-stressed animals challenged with cocaine.