title: Effects of oxytocin on methamphetamine-seeking exacerbated by predator odor pre-exposure in rats.
abstract: BACKGROUND
  The endogenous oxytocin system has emerged as an inhibitor of drug-seeking and stress in preclinical models.
  
  
  OBJECTIVE
  The goal of this study was to examine whether systemic oxytocin administration attenuated methamphetamine (METH)-seeking in rats pre-exposed to a predator odor threat.
  
  
  METHODS
  In Experiment 1, rats were exposed for 5 days to the predator odor, 2,5-dihydro-2,4,5-trimethylthiazoline (TMT), or saline before METH self-administration began. After extinction training, rats were injected with 1 mg/kg, ip oxytocin (OXT) or saline 30 min before a cue-induced reinstatement test followed by re-extinction and a TMT-induced reinstatement test. In Experiment 2, TMT pre-exposure was followed by 10 days of 1 mg/kg OXT or saline injections before METH self-administration, extinction, and a TMT-induced reinstatement test.
  
  
  RESULTS
  In Experiment 1, TMT pre-exposed rats that were injected with saline 30 min before reinstatement exhibited greater drug-seeking induced by conditioned cues or TMT than that exhibited by saline pre-exposed rats. A single injection of OXT 30 min before reinstatement suppressed METH-seeking in both saline- and TMT pre-exposed rats. In Experiment 2, TMT pre-exposed rats that received saline injections for 10 days prior to METH self-administration exhibited enhanced drug-seeking induced by TMT during stress-induced reinstatement. OXT injections for 10 days prior to METH self-administration blocked only the stress-induced exacerbation of drug-seeking in TMT pre-exposed rats.
  
  
  CONCLUSIONS
  These results support further research on the development of oxytocin as a novel therapeutic drug that has enduring effects on drug-seeking exacerbated by stress.
authors.affiliation: Department of Neuroscience, Medical University of South Carolina, 173 Ashley Ave, MSC 510, Charleston, SC, 29425, USA.
authors.forename: Chantelle L
authors.initials: CL
authors.lastname: Ferland
authors.affiliation: Department of Neuroscience, Medical University of South Carolina, 173 Ashley Ave, MSC 510, Charleston, SC, 29425, USA.
authors.forename: Carmela M
authors.initials: CM
authors.lastname: Reichel
authors.affiliation: Department of Neuroscience, Medical University of South Carolina, 173 Ashley Ave, MSC 510, Charleston, SC, 29425, USA. mcginty@musc.edu.
authors.forename: Jacqueline F
authors.initials: JF
authors.lastname: McGinty
mesh_terms: D000818:Animals; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D003463:Cues; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage*; D009812:Odorants; D010121:Oxytocin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration; D013844:Thiazoles / Q000494:pharmacology
chemical_list: C411827:2,5-dihydro-2,4,5-trimethylthiazoline; D000697:Central Nervous System Stimulants; D013844:Thiazoles; D008694:Methamphetamine; D010121:Oxytocin
keywords: Addiction; Methamphetamine; Oxytocin; PTSD; Predator odor; Reinstatement; Self-administration; Stress; Substance use disorder