title: Oxytocin Acts in Nucleus Accumbens to Attenuate Methamphetamine Seeking and Demand.
abstract: Evidence indicates that oxytocin, an endogenous peptide well known for its role in social behaviors, childbirth, and lactation, is a promising addiction pharmacotherapy. We employed a within-session behavioral-economic (BE) procedure in rats to examine oxytocin as a pharmacotherapy for methamphetamine (meth) addiction. The BE paradigm was modeled after BE procedures used to assess motivation for drugs in humans with addiction. The same BE variables assessed across species have been shown to predict later relapse behavior. Thus, the translational potential of preclinical BE studies is particularly strong.
  
  
  
  We tested the effects of systemic and microinfused oxytocin on demand for self-administered intravenous meth and reinstatement of extinguished meth seeking in male and female rats using a BE paradigm. Correlations between meth demand and meth seeking were assessed.
  
  
  
  Female rats showed greater demand (i.e., motivation) for meth compared with male rats. In both male and female rats, meth demand predicted reinstatement of meth seeking, and systemic oxytocin decreased demand for meth and attenuated reinstatement to meth seeking. Oxytocin was most effective at decreasing meth demand and seeking in rats with the strongest motivation for drug. Finally, these effects of systemic oxytocin were mediated by actions in the nucleus accumbens.
  
  
  
  Oxytocin decreases meth demand and seeking in both sexes, and these effects depend on oxytocin signaling in the nucleus accumbens. Overall, these data indicate that development of oxytocin-based therapies may be a promising treatment approach for meth addiction in humans.
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina. Electronic address: brittney.cox@uci.edu.
authors.forename: Brittney M
authors.initials: BM
authors.lastname: Cox
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Brandon S
authors.initials: BS
authors.lastname: Bentzley
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Helaina
authors.initials: H
authors.lastname: Regen-Tuero
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina; Department of Psychology, Westmont College, Santa Barbara, California.
authors.forename: Ronald E
authors.initials: RE
authors.lastname: See
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Carmela M
authors.initials: CM
authors.lastname: Reichel
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina; Brain Health Institute, Rutgers University/Rutgers Biomedical and Health Sciences, Piscataway, New Jersey.
authors.forename: Gary
authors.initials: G
authors.lastname: Aston-Jones
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D005108:Extinction, Psychological / Q000187:drug effects; D057967:Infusions, Intraventricular; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D008845:Microinjections; D009042:Motivation / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000187:drug effects*; D010121:Oxytocin / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D012646:Self Administration
chemical_list: D008694:Methamphetamine; D010121:Oxytocin
keywords: Addiction; Behavioral economics; Methamphetamine; Oxytocin; Reinstatement; Self-administration