title: Stress and cocaine interact to modulate Arc/Arg3.1 expression in rat brain.
abstract: BACKGROUND
  The interaction between stress and drugs of abuse is a critical component of drug addiction, but the underlying molecular mechanisms remain elusive. Arc/Arg3.1 is an effector immediate early gene that may represent a bridge connecting short- and long-term neuronal modifications associated with exposure to stress and drugs of abuse.
  
  
  OBJECTIVE
  This research aims to study the modulation of Arc/Arg3.1 expression as a marker of neuronal changes associated with exposure to stress and cocaine.
  
  
  METHODS
  Rats exposed to either single or repeated stress sessions were subjected to a single intraperitoneal injection of cocaine hydrochloride (10 mg/kg) and sacrificed 2 h later. RNase protection assay was used to determine changes in Arc/Arg3.1 gene expression in different brain regions.
  
  
  RESULTS
  We found significant stress-cocaine interactions in the prefrontal cortex (p < 0.001) and hypothalamus (p < 0.05). In the prefrontal cortex, acute stress potentiated cocaine-induced Arc/Arg3.1 mRNA elevation, whereas prolonged stress attenuated the response to cocaine. In the hypothalamus, although markedly reduced by acute stress, Arc/Arg3.1 gene expression was still increased by cocaine. No interaction was observed following repeated stress. Notably, cocaine-induced Arc/Arg3.1 mRNA levels were not influenced by stress in striatum and hippocampus.
  
  
  CONCLUSIONS
  In our experimental model, stress interacted with cocaine to alter Arc/Arg3.1 expression in a regionally selective fashion and in a way that depended on whether stress was acute or repeated. These results point to Arc/Arg3.1 as a potential molecular target modulated by stress to alter cellular sensitivity to cocaine.
authors: Department of Pharmacological Sciences, Center of Neuropharmacology, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milan, Italy.
authors: Lucia
authors: L
authors: Caffino
authors: Giorgio
authors: G
authors: Racagni
authors: Fabio
authors: F
authors: Fumagalli
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