Effects of oxytocin on methamphetamine-seeking exacerbated by predator odor pre-exposure in rats.

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.

journal_title

Psychopharmacology

authors

Ferland CL,Reichel CM,McGinty JF

doi

10.1007/s00213-015-4184-7

subject

Has Abstract

pub_date

2016-03-01 00:00:00

pages

1015-24

issue

6

eissn

0033-3158

issn

1432-2072

pii

10.1007/s00213-015-4184-7

journal_volume

233

pub_type

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