IFEC   20925
INSTITUTO DE FARMACOLOGIA EXPERIMENTAL DE CORDOBA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
A long term stress-induced sensitization to cocaine is associated with opposite changes in AMPA receptors and cocaine-induced glutamate release in nucleus accumbens
Autor/es:
GARCÍA KELLER, C; MARTÍNEZ, S; ESPARZA, A; CANCELA, L.M
Lugar:
Mar del Plata
Reunión:
Congreso; XLII Reunión Científica anual de la Sociedad Argentina de Farmacología Experimental (SAFE); 2010
Resumen:
Cocaine induces behavioural and molecular sensitization in both, the dopaminergic (DA) and glutamatergic (Glu) mesocorticolimbic systems. It has been shown that glutamatergic mechanisms are involved in the development of stress-induced sensitization to behavioural and neurochemical effects of psychostimulants (Pacchioni et al., 2007). The aim of this work was to study the cocaine-induced DA and Glu release as well as the AMPA receptor (AMPAR) surface expression in Nucleus Accumbens Core and Shell (NAc and NAs), from pre-stressed animals. Male Wistar rats (250-350 g) were restrained for 2 h while control animals were left undisturbed in their cages. Twenty-one days after stress, all animals were assigned to one of the following experiments: I) Microdialysis: DA and Glu levels were determinated by HPLC in NAc and NAs in response to saline and cocaine (15mg/kg ip). II) AMPAR expression in NA after saline or cocaine (15 mg/kg i.p.). The animals were decapitated 45 min after the injections, the NA was dissected and the surface fraction was subjected to quantitative immunoblotting for AMPAR using anti-GluR1, as primary antibody. Our results demonstrate that in NAc from pre-stressed animals, the cocaine-induced DA release was clearly augmented meanwhile the drug-induced Glu release was decreased as regard to the values observed in the non-stress group. Since the AMPAR surface expression was increased in NA from pre-stressed animals, it is conceivable to think that an homeostatic compensatory mechanism opposes to the decrease in Glu release. It should be noted that, the mechanism implied in the increase of AMPAR following withdrawal of a cocaine sensitization regime, is yet unknown. These findings are discussed in the framework that relevant plastic changes are common between the stress and drug-induced sensitization whereas another seem to be differently triggered for each one of these factors.