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

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

Cancún

Congreso; ISN-ASN; 2013

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 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. On day 16 following the stress episode, animals from non-stress and stress groups were randomly divided in two groups which were administered with five daily injections of vehicle or ceftriaxone (200 mg/kg). Twenty-four hours later the last injection, the locomotor activity response to saline or cocaine (15 mg/kg i.p.) was evaluated for 45 min and then, the animals were sacrificed to determine GLT-1 expression for western blot in NAc Core.Our results demonstrate that ceftriaxome abrogated the stress-induced cross-sensitization to cocaine. The results will be discussed in the context of the influence of ceftriaxome on the stress-induced changes on GLT-1 and glutamate homeostasis in nucleus accumbens core.