Restraint stress-induced changes on glutamate homeostasis in nucleus accumbens core are related to alterations in GLT-1

GARCÍA KELLER, C; ESPARZA, A; KALIVAS, PW; CANCELA, L.M

Valparaiso

Workshop; II International Workshop: "Motivated behavior, stress and addiction"; 2012

LARNEDA

Sensitization is associated with neuroplasticity in the dopaminergic (DA) and glutamatergic (Glu) mesocorticolimbic systems.It is well known thatwithdrawal (2-3 weeks) from chronic cocaine,disrupted Glu homeostasis and decreasedglutamate 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 wasto evaluateif stress-induced alterations in Glu 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 the stress episode, the following experiments were performed: I) Microdialysis: basal Glu release was measured by HPLC in NAc Core and Shell by no-net-flux techniqueII) Western blot: for GLT-1 expression in NAc Coreafter i.p. injection of saline or cocaine (15 mg/kg). Another non-stress and stress groups of animals were randomly divided in two groups since day 16 following the stress episode: 1) Five daily injections of vehicle or ceftriaxone (200 mg/kg) were administered andtwenty-four hours later the locomotor activitywas registered in response to saline or cocaine (15 mg/kg i.p.)for 45 min. Our results demonstrate that pre-stressed animalsshowed 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 pre-treated with ceftriaxone. We speculate that ceftriaxone might restore glutamate homeostasisin pre-stressed animals.