title: ELAV-GAP43 pathway activation following combined exposure to cocaine and stress.
abstract: BACKGROUND
  An increasing body of evidence suggests that drug addiction engages circuits also associated with memory processes. In particular, in the hippocampus, a substantial similarity seems to exist between the changes yielded by drugs of abuse and those induced by hippocampal-dependent learning.
  
  
  OBJECTIVE
  Considering the key involvement of neuronal Embryonic Lethal Abnormal Vision (nELAV) proteins in memory processes occurring within the hippocampus and the critical role of stress for compulsive drug use and relapse, we investigated the effect of cocaine and stress challenges on the activation of the nELAV cascade.
  
  
  METHODS
  Rats were treated subcutaneously with vehicle or cocaine hydrochloride (20 mg/kg, once a day for 2 weeks). Three days later, half of them were also subjected to a single stress exposure. Western blotting and real-time polymerase chain reaction (PCR) experiments were performed on the hippocampi.
  
  
  RESULTS
  Our results show that the combination of repeated exposure to cocaine and acute stress significantly enhances nELAV expression and phosphorylation in the hippocampus with a concomitant increase of GAP43 expression (a specific nELAV target), an effect that seems to involve, upstream, protein kinase C alpha (PKCα). The activation of this pathway occurs independently from widespread neuronal activation since no alterations were observed in the expression of the immediate early gene Arc (a widely established index of neuronal activity), suggesting that the activation of the nELAV-GAP43 cascade reflects a targeting of specific processes rather than a global interference with hippocampal homeostasis.
  
  
  CONCLUSIONS
  Based on our results, we speculate that cocaine and stress may recruit such a pathway, crucial for physiological learning, potentially contributing to the aberrant engagement of learning mechanisms observed in drug addiction behavior.
authors.affiliation: Department of Experimental and Applied Pharmacology, Centre of Excellence in Applied Biology, University of Pavia, Via Taramelli 14, 27100 Pavia, Italy. alessia.pascale@unipv.it
authors.forename: Alessia
authors.initials: A
authors.lastname: Pascale
authors.forename: Marialaura
authors.initials: M
authors.lastname: Amadio
authors.forename: Lucia
authors.initials: L
authors.lastname: Caffino
authors.forename: Giorgio
authors.initials: G
authors.lastname: Racagni
authors.forename: Stefano
authors.initials: S
authors.lastname: Govoni
authors.forename: Fabio
authors.initials: F
authors.lastname: Fumagalli
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000235:genetics; D051959:ELAV Proteins / Q000235:genetics / Q000378:metabolism*; D019922:GAP-43 Protein / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007279:Injections, Subcutaneous; D008297:Male; D009474:Neurons / Q000378:metabolism; D016133:Polymerase Chain Reaction; D051571:Protein Kinase C-alpha / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological
chemical_list: D051959:ELAV Proteins; D019922:GAP-43 Protein; D051571:Protein Kinase C-alpha; D003042:Cocaine