Faculty Collaboration Database

Corticosterone Potentiation of Cocaine-Induced Reinstatement of Conditioned Place Preference in Mice is Mediated by Blockade of the Organic Cation Transporter 3. Neuropsychopharmacology 2017 Feb;42(3):757-765

Date

09/09/2016

Pubmed ID

27604564

Pubmed Central ID

PMC5240184

DOI

10.1038/npp.2016.187

Scopus ID

2-s2.0-84990940925 (requires institutional sign-in at Scopus site)   23 Citations

Abstract

The mechanisms by which stressful life events increase the risk of relapse in recovering cocaine addicts are not well understood. We previously reported that stress, via elevated corticosterone, potentiates cocaine-primed reinstatement of cocaine seeking following self-administration in rats and that this potentiation appears to involve corticosterone-induced blockade of dopamine clearance via the organic cation transporter 3 (OCT3). In the present study, we use a conditioned place preference/reinstatement paradigm in mice to directly test the hypothesis that corticosterone potentiates cocaine-primed reinstatement by blockade of OCT3. Consistent with our findings following self-administration in rats, pretreatment of male C57/BL6 mice with corticosterone (using a dose that reproduced stress-level plasma concentrations) potentiated cocaine-primed reinstatement of extinguished cocaine-induced conditioned place preference. Corticosterone failed to re-establish extinguished preference alone but produced a leftward shift in the dose-response curve for cocaine-primed reinstatement. A similar potentiating effect was observed upon pretreatment of mice with the non-glucocorticoid OCT3 blocker, normetanephrine. To determine the role of OCT3 blockade in these effects, we examined the abilities of corticosterone and normetanephrine to potentiate cocaine-primed reinstatement in OCT3-deficient and wild-type mice. Conditioned place preference, extinction and reinstatement of extinguished preference in response to low-dose cocaine administration did not differ between genotypes. However, corticosterone and normetanephrine failed to potentiate cocaine-primed reinstatement in OCT3-deficient mice. Together, these data provide the first direct evidence that the interaction of corticosterone with OCT3 mediates corticosterone effects on drug-seeking behavior and establish OCT3 function as an important determinant of susceptibility to cocaine use.

Author List

McReynolds JR, Taylor A, Vranjkovic O, Ambrosius T, Derricks O, Nino B, Kurtoglu B, Wheeler RA, Baker DA, Gasser PJ, Mantsch JR

Authors

Paul Gasser BS,MS,PhD Assistant Professor in the Biomedical Sciences department at Marquette University
John Mantsch PhD Chair, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Cocaine
Conditioning, Classical
Corticosterone
Dopamine Uptake Inhibitors
Male
Mice
Mice, Inbred C57BL
Normetanephrine
Octamer Transcription Factor-3