STUDY OF THE LONG-TERM INFLUENCE OF A SINGLE RESTRAINT STRESS ON GLUTAMATE UPTAKE AND SYNAPTIC PLASTICITY IN NUCLEUS ACCUMBENS
García Keller, C.*; Esparza, A.*; Bollati F.*; Gipson, C#; Kupichnik, Y#; Brown, R#; Kalivas, P.W#; 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.
#Department of Neurosciences, MUSC, Charleston, South Carolina.
Disrupted glutamate homeostasis is observed 21 days later in the nucleus accumbens (NA) core, but not shell, following a single session of restraint stress. The hallmarks of this homeostatic dysregulation are that basal levels of glutamate are increased, about 5.33 µM in pre-stressed animals compared to 2.09 µM from the control group, meanwhile the synaptic glutamate released during cocaine challenge decreased in pre-stressed as compared to non-stressed animals (Garcia-Keller, et al 2012). The aim of our study was to determine in the cross-sensitization model of stress and cocaine the following: I) Firstly, the functionality and expression of glutamate transporter GLT-1 and synaptic plasticity by measuring AMPA/NMDA ratio in the NA core. II) Secondly, to determine whether ceftriaxone (200 mg/kg i.p) can restore compromised glutamate transport and reverse alterations in synaptic plasticity in pre-stressed animals. 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 animals were sacrificed to determine GLT-1 expression or functionality (by western blot or glutamate uptake) in NA core, and synaptic plasticity (AMPA/NMDA ratio) in NA. Our results demonstrate that ceftriaxone restores the altered glutamate homeostasis increasing the functionality and the expression of the GLT-1 in the pre-stressed animals, but there was no change in synaptic plasticity showed by the AMPA/NMDA ratio with only 5 days ceftriaxone treatment in the stressed rats.
