title: Oxytocin reduces cocaine seeking and reverses chronic cocaine-induced changes in glutamate receptor function.
abstract: BACKGROUND
  Oxytocin, a neurohypophyseal neuropeptide, is a potential mediator and regulator of drug addiction. However, the cellular mechanisms of oxytocin in drug seeking remain unknown.
  
  
  METHODS
  In the present study, we used a self-administration/reinstatement model to study the effects of oxytocin on cocaine seeking and its potential interaction with glutamate function at the receptor level.
  
  
  RESULTS
  Systemic oxytocin dose-dependently reduced cocaine self-administration during various schedules of reinforcement, including fixed ratio 1, fixed ratio 5, and progressive ratio. Oxytocin also attenuated reinstatement to cocaine seeking induced by cocaine prime or conditioned cues. Western-blot analysis indicated that oxytocin increased phosphorylation of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptor GluA1 subunit at the Ser 845 site with or without accompanying increases in phosphorylation of extracellular signal-regulated kinase, in several brain regions, including the prefrontal cortex, bed nucleus of the stria terminalis, amygdala, and dorsal hippocampus. Immunoprecipitation of oxytocin receptor and GluA1 subunit receptors further demonstrated a physical interaction between these 2 receptors, although the interaction was not influenced by chronic cocaine or oxytocin treatment. Oxytocin also attenuated sucrose seeking in a GluA1- or extracellular-signal-regulated kinase-independent manner.
  
  
  CONCLUSIONS
  These findings suggest that oxytocin mediates cocaine seeking through interacting with glutamate receptor systems via second messenger cascades in mesocorticolimbic regions.
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina (Drs Zhou, Sun, Young, Lee, McGinty, and See).
authors.forename: Luyi
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina (Drs Zhou, Sun, Young, Lee, McGinty, and See).
authors.forename: Wei-Lun
authors.initials: WL
authors.lastname: Sun
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina (Drs Zhou, Sun, Young, Lee, McGinty, and See).
authors.forename: Amy B
authors.initials: AB
authors.lastname: Young
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina (Drs Zhou, Sun, Young, Lee, McGinty, and See).
authors.forename: Kunhee
authors.initials: K
authors.lastname: Lee
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina (Drs Zhou, Sun, Young, Lee, McGinty, and See).
authors.forename: Jacqueline F
authors.initials: JF
authors.lastname: McGinty
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina (Drs Zhou, Sun, Young, Lee, McGinty, and See). seere@musc.edu.
authors.forename: Ronald E
authors.initials: RE
authors.lastname: See
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D002491:Central Nervous System Agents / Q000494:pharmacology*; D003042:Cocaine / Q000008:administration & dosage; D019970:Cocaine-Related Disorders / Q000188:drug therapy* / Q000503:physiopathology; D019422:Dietary Sucrose / Q000008:administration & dosage; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D058999:Drug-Seeking Behavior / Q000187:drug effects* / Q000502:physiology; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D008297:Male; D010121:Oxytocin / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism*; D012055:Reinforcement Schedule; D012646:Self Administration
chemical_list: D002491:Central Nervous System Agents; D003042:Cocaine; D019422:Dietary Sucrose; D018765:Dopamine Uptake Inhibitors; D048049:Extracellular Signal-Regulated MAP Kinases; D010121:Oxytocin; D018091:Receptors, AMPA
keywords: cocaine; glutamate receptor; oxytocin; reinstatement; self-administration.