COCAINE DECREASES ABPs PHOSPHORILATION AND INCREASES AMPA SURFACE EXPRESSION IN RAT NUCLEUS ACCUMBENS FOLLOWING CHRONIC STRESS

ESPARZA MA; AVALOS, M.P.; CONSTANZA GARCÍA-KELLER; MIRIAM VIRGOLINI; CALFA G; CANCELA LM.

Córdoba

Encuentro; V Encuentro de Jóvenes Investigadores en Neurociencias de Córdoba; 2013

Behavioral sensitization is an example of experience-dependent plasticity, induced by drug or stress, which has been suggested to involve plasticity at glutamatergic synapses and there is evidence for a common mechanism triggered by stress and drugs at excitatory synapses on midbrain dopamine neurons. These experiments evaluated how the expression of stress-induced sensitization to cocaine (15 mg/kg i.p.) is associated to alterations in actin binding proteins (ABPs) and the surface expression of GluR1 in nucleus accumbens (NAc). Male wistar rats were restrained daily (2 hours) for 7 days, and three weeks later, the NAc was dissected 45 min following acute saline or cocaine (30 mg/kg i.p. or 15 mg/Kg). F-actin, ABPs and AMPAR were determined by western blotting. Locomotor activity was monitored in a photocell apparatus and quantified as total photocell counts. For these sessions, animals were allowed to habituate to the activity chambers before latrunculin A or DMSO (1%) microinjections, which were followed by cocaine (15 mg/kg, i.p.) or saline. Our experiments revealed a decrease in p-cofilin and pcortactin, and an increase in GluR1, in the stress plus cocaine group as was previously shown after cocaine (30 mg/kg). The stress-induced sensitization to cocaine was prevented by either latrunculin A or CNQX. Interestingly, latrunculin A also reversed the stress/cocaine-induced increase in GluR1. This study shows that a history of repeated stress alters the ability of a subsequent cocaine injection to modulate the reorganization of synaptic connections, actin cytoskeleton and AMPAR expression in the NAc. Grants: FONCyT, SECyT, CONICET.