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

CONSTANZA GARCIA KELLER; ESPARZA ALEJANDRA; MONGI BRAGATO BETHANIA; KALIVAS PETER; CANCELA LILIANA

Valparaíso

Workshop; II International Workshop Motivated behavior, stress and addiction: from molecules to behavior; 2012

Sensitization is associated with neuroplasticity in the dopaminergic (DA) andglutamatergic (Glu) mesocorticolimbic systems. It is well known that withdrawal (2-3 weeks)from chronic cocaine, disruptedGlu homeostasis and decreased glutamatetransporter-1 (GLT-1) expression in the nucleus accumbens (NAc) core; and thatthese changes were restored with ceftriaxone treatment. The aim of our study was to evaluate if stress-inducedalterations in Glu homeostasis and GLT-1, andif these changes can be restored with ceftriaxone pre-treatment. Male Wistar rats (250-350 g) were restrained for twohours, while control animals were left undisturbed in their cages. Twenty-onedays after the stress episode, the following experiments were performed: I)Microdialysis: basal Glu release was measured by HPLC in NAc Core and Shell byno-net-flux technique II) Western blot: for GLT-1 expression in NAc Core after i.p.injection of saline or cocaine (15 mg/kg). Another non-stress and stress groupsof animals were randomly divided in two groups since day 16 following thestress episode: 1) Five daily injections of vehicle or ceftriaxone (200 mg/kg)were administered and twenty-four hours later the locomotor activity wasregistered in response to saline or cocaine (15 mg/kg i.p.) for 45 min.Our results demonstrate that pre-stressed animals showed increased basallevels of Glu in Core, but not shell, and that this could be related to a decreasedexpression of GLT-1 in NAc. Interestingtly, the expression of stress-induced behavioralsensitization was abrogated when animals were pre-treated with ceftriaxone. Wespeculatethat ceftriaxone might restore glutamate homeostasis in pre-stressed animals.