INVESTIGADORES
VIRGOLINI Miriam Beatriz
congresos y reuniones científicas
Título:
Stress-Induced Sensitization to Cocaine: Effects of Stress and Cocaine on ABPs, Surface GluR1, PSD size and Dendritic Spines in the NAc
Autor/es:
10. ESPARZA, M.A.; GARCIA KELLER, C.; VIRGOLINI, M.; KALIVAS P.W.; CANCELA L.M.
Lugar:
Buenos Aires (Argentina) y Montevideo (Uruguay)
Reunión:
Congreso; International Society for Neurochemistry. Joint ISN School for Neurochemistry. 2nd Latin American School of Advanced Neurochemistry: The synapse in health and disease.; 2012
Institución organizadora:
ISN
Resumen:
Drug addiction is associated with
long-term changes in the synaptic function, including the actin cytoskeleton.
There is evidence about the proactive influence of stress on drug addiction a
process that is exerted on excitatory synapses by the activation of common
mechanisms between drugs and stress. The present study investigated whether the
neurobiological mechanisms that modulate repeated cocaine administration also
occur in a stress-induced cocaine sensitization model. These experiments
evaluated whether repeated stress induces alterations in actin rearrangement,
AMPA receptors (AMPAR) expression and the size of postsynaptic density (PSD) in the nucleus accumbens (NAc). Wistar rats were restrained daily (2
hours) for 7 days, and three weeks later, the NAc was dissected from animals 45
min following acute saline or cocaine administration. F-actin, actin-binding
protein (ABP) and AMPAR
were
determined by western
blotting, and dendritic
spines and the size of PSD measured by electron microscopy. Locomotor activity was monitored in
a photocell apparatus (actographs). For these sessions, animals were allowed to
habituate to the activity chambers for 60 min before latrunculin A, CNQX or
DMSO (1%) microinjections, which were followed by cocaine or saline, and behavior recorded was for 120
min. Our experiments
revealed that repeated stress induces changes in actin and actin binding
proteins. In the NAc, a decrease in p-cofilin and p-cortactin, concomitant to
an increase in AMPAR and the size of PSD, was found in the stress plus cocaine
group. The stress-induced sensitization to cocaine was prevented by
administering either
latrunculin A or CNQX.
Interestingly, latrunculin A in the NAc also reversed the stress/cocaine-induced
increase in GluR1, indicating a potential role for actin cycling in the
increased AMPAR accompanying cocaine cross-sensitization. This study shows that
stress-induced changes in the actin cytoskeleton, the size of PSD and AMPAR
partly parallel the alterations elicited by sensitization to repeated cocaine
and that actin dynamics regulate AMPAR expression in the NAc and underlie the
expression of cross-sensitization between stress and cocaine.