Faculty Collaboration Database

Stress-induced sensitization to cocaine: actin cytoskeleton remodeling within mesocorticolimbic nuclei. Eur J Neurosci 2012 Oct;36(8):3103-17

Date

08/14/2012

Pubmed ID

22882295

Pubmed Central ID

PMC4346257

DOI

10.1111/j.1460-9568.2012.08239.x

Scopus ID

2-s2.0-84867555380 (requires institutional sign-in at Scopus site)   25 Citations

Abstract

This study investigated the consequence of repeated stress on actin cytoskeleton remodeling in the nucleus accumbens (NAc) and prefrontal cortex (Pfc), and the involvement of this remodeling in the expression of stress-induced motor cross-sensitization with cocaine. Wistar rats were restrained daily (2 h) for 7 days and, 3 weeks later, their NAc and Pfc were dissected 45 min after acute saline or cocaine (30 mg/kg i.p.). F-actin, actin-binding proteins (ABP) and GluR1 were quantified by Western blotting, and dendritic spines and postsynaptic density (PSD) size measured by electron microscopy. In the NAc from the stress plus cocaine group we observed a decrease in the phosphorylation of two ABPs, cofilin and cortactin, and an increase in the PSD size and the surface expression of GluR1, consistent with a more highly branched actin cytoskeleton. The Pfc also showed evidence of increased actin polymerization after stress as an increase was observed in Arp2, and in the number of spines. Inhibiting actin cycling and polymerization with latrunculin A into the NAc, but not the Pfc, inhibited the expression of cross-sensitization to cocaine (15 mg/kg i.p.) and restored the expression of GluR1 to control levels. This study shows that a history of repeated stress alters the ability of a subsequent cocaine injection to modulate dendritic spine morphology, actin dynamics and GluR1 expression in the NAc. Furthermore, by regulating GluR1 expression in the NAc, elevated actin cycling contributes to the expression of cross-sensitization between stress and cocaine, while stress-induced changes in the Pfc were not associated with cross-sensitization.

Author List

Esparza MA, Bollati F, Garcia-Keller C, Virgolini MB, Lopez LM, Brusco A, Shen HW, Kalivas PW, Cancela LM

Author

Constanza Garcia Keller PhD Assistant Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Actin Cytoskeleton
Actin Depolymerizing Factors
Actins
Animals
Bridged Bicyclo Compounds, Heterocyclic
Central Nervous System Sensitization
Cocaine
Cortactin
Dendritic Spines
Gene Expression
Male
Motor Activity
Nucleus Accumbens
Phosphorylation
Polymerization
Post-Synaptic Density
Prefrontal Cortex
Rats
Rats, Wistar
Receptors, AMPA
Restraint, Physical
Stress, Psychological
Thiazolidines