Chantelle L Ferland1, Carmela M Reichel1, Jacqueline F McGinty2. 1. Department of Neuroscience, Medical University of South Carolina, 173 Ashley Ave, MSC 510, Charleston, SC, 29425, USA. 2. Department of Neuroscience, Medical University of South Carolina, 173 Ashley Ave, MSC 510, Charleston, SC, 29425, USA. mcginty@musc.edu.
Abstract
RATIONALE: The endogenous oxytocin system has emerged as an inhibitor of drug-seeking and stress in preclinical models. OBJECTIVES: 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.
RATIONALE: The endogenous oxytocin system has emerged as an inhibitor of drug-seeking and stress in preclinical models. OBJECTIVES: 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: Joseph O Ojo; M Banks Greenberg; Paige Leary; Benoit Mouzon; Corbin Bachmeier; Michael Mullan; David M Diamond; Fiona Crawford Journal: Front Behav Neurosci Date: 2014-06-23 Impact factor: 3.558
Authors: Marek Schwendt; John Shallcross; Natalie A Hadad; Mark D Namba; Helmut Hiller; Lizhen Wu; Eric G Krause; Lori A Knackstedt Journal: Transl Psychiatry Date: 2018-10-05 Impact factor: 6.222