Stress-induced cocaine sensitization: Changes in the actin cytoskeleton and in dendritic spines from prefrontal cortex

L. M. CANCELA, A. ESPARZA, F. BOLLATI, C. GARCIA KELLER, M. VIRGOLINI, M. LOPEZ, A.BRUSCO, P. W. KALIVAS

Chicago USA

Congreso; 2009 Neuroscience Meeting Planner. Chicago, IL: Society for Neuroscience, 2009.; 2009

Society for Neuroscience

Drug addiction is associated with long-term changes in synaptic functionality. The proactive influence of stress on drug-addiction is exerted on excitatory synapses through the activation of common mechanisms between stress and drugs. This study aimed to show whether the neurobiological mechanisms that modulate repeated-cocaine administration also occur in a chronic stress-induced cocaine sensitization model. Considering that F-actin is involved in the dendritic spine formation, it was evaluated whether chronic restraint stress and a challenge with cocaine, induce long-term alterations in both, actin rearrangement and dendritic spine density in prefrontal cortex. Wistar rats (250-330 g) were restrained daily during 2 h for seven consecutive sessions. Twenty-one days after the stress, the animals were injected with cocaine (30 mg/kg i.p.) or saline and 45 min after perfused for electron microscopy studies, or decapitated to obtain brain tissue for immunoblotting. The density of spines (number of spines per µm2) was analyzed by electron microscopy, in 40 fields (42.52 µm2) for each animal of each experimental group. It was shown that chronic restraint stress induces a significant increase in F-actin levels in prefrontal cortex, which returned to baseline after cocaine administration. The polymerizing protein Arp2 was also increased while the depolymerizing p-cofilin was not modified after chronic stress. Postsynaptic density proteins such as homer and GluR1 were not changed after repeated stress and/or cocaine. The analysis of the density of spines in prefrontal cortex showed an increase after chronic stress, and a return to baseline values following stress and cocaine, similarly to that observed for F-actin. Our findings revealed that chronic stress induces changes in protein levels involved in synaptic plasticity, such as actin and proteins that regulate actin cytoskeleton, known as actin-binding proteins. It is highly probable that chronic stress-induced changes on F-actin and spines are associated with the cross-sensitization to cocaine.