title: Glucocorticoid receptors in dopaminoceptive neurons, key for cocaine, are dispensable for molecular and behavioral morphine responses.
abstract: BACKGROUND
  Psychostimulants and opiates trigger similar enduring neuroadaptations within the reward circuitry thought to underlie addiction. Transcription factors are key to mediating these enduring behavioral alterations. The facilitation of these maladaptive changes by glucocorticoid hormones suggests that the glucocorticoid receptor (GR), a transcription factor involved in the stress response, could be a common mediator of responses to pharmacologically distinct classes of abused drugs.
  
  
  METHODS
  We employed mouse models carrying GR gene inactivation in either dopamine or dopaminoceptive neurons to determine the involvement of this transcription factor in behavioral responses to cocaine and morphine. We then combined microarray analysis, drug-elicited immediate early gene induction, and in vivo microdialysis to elucidate the molecular underpinnings of these responses.
  
  
  RESULTS
  Inactivating GR within dopaminoceptive neurons markedly reduces cocaine-induced conditioned place preference and the expression of locomotor sensitization. In striking contrast, GR had no effect on behavioral morphine responses in either dopaminoceptive or dopamine neurons. The dopaminoceptive mutation engenders alterations in the expression of striatal genes that are implicated in glutamatergic transmission and plasticity. Within the nucleus accumbens, impaired cellular responses to cocaine are conspicuous; a pronounced deficit in cocaine-elicited extracellular dopamine release, expression of the key IEGs c-Fos and Zif268, and phosphorylation of extracellular signal-regulated kinases 1/2 in mutants were observed. In contrast, these molecular and neurochemical changes were not observed in response to morphine, mirroring the lack of effect on behavioral responses to morphine.
  
  
  CONCLUSIONS
  Combined behavioral and molecular approaches have identified a subset of neurons in which GR differentially influences cocaine- and morphine-induced responses.
authors.affiliation: Centre National de la Recherche Scientifique Unité Mixte de Recherche 7224, Physiopathologie des Maladies du Système Nerveux Central, Molecular Genetics, Neurophysiology and Behavior Group, Paris, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Barik
authors.forename: Sébastien
authors.initials: S
authors.lastname: Parnaudeau
authors.forename: Aurélie Lampin
authors.initials: AL
authors.lastname: Saint Amaux
authors.forename: Bruno P
authors.initials: BP
authors.lastname: Guiard
authors.forename: Jose Felipe
authors.initials: JF
authors.lastname: Golib Dzib
authors.forename: Olivier
authors.initials: O
authors.lastname: Bocquet
authors.forename: Alain
authors.initials: A
authors.lastname: Bailly
authors.forename: Arndt
authors.initials: A
authors.lastname: Benecke
authors.forename: François
authors.initials: F
authors.lastname: Tronche
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000378:metabolism*; D003042:Cocaine / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D020868:Gene Silencing; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D009020:Morphine / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D012054:Reinforcement, Psychology; D019966:Substance-Related Disorders / Q000378:metabolism*
chemical_list: D002492:Central Nervous System Depressants; D011965:Receptors, Glucocorticoid; D009020:Morphine; D003042:Cocaine; D004298:Dopamine