Journal article
Modulation of OCT3 expression by stress, and antidepressant-like activity of decynium-22 in an animal model of depression
Pharmacology, biochemistry and behavior, Vol.131, pp.33-41
04/2015
DOI: 10.1016/j.pbb.2015.01.004
PMID: 25597272
Abstract
The organic cation transporter-3 (OCT3) is a glucocorticoid-sensitive uptake mechanism that has been shown to regulate the bioavailability of monoamines in brain regions that are implicated in the pathophysiology of depression. In the present study, the relative impacts of acute stress alone and acute stress with a history of repeated stress (chronic+acute) were evaluated in two strains of rats: the stress-vulnerable Wistar-Kyoto (WKY) strain and the somewhat more stress-resilient Long-Evans (LE) strain. OCT3 mRNA was significantly upregulated in the hippocampus of LE rats 2h after exposure to acute restraint stress, but not in acutely-restrained rats with a history of repeated social defeat stress. WKY rats exhibited a very different pattern. OCT3 mRNA was unaffected by acute restraint stress alone but was robustly upregulated after repeated+acute stress. There was also a corresponding increase in cytosolic OCT3 protein following repeated+acute stress in WKY rats 3h after presentation of the acute stressor. These results are consistent with the hypothesis that altered expression of the OCT3 may play a role in stress coping, and strain differences in regulation of this expression may contribute to differences in physiological and behavioral responses to stress. Furthermore, the OCT3 inhibitor, decynium 22 (1 and 10μg/kg, i.p.) reduced immobility of WKY rats, but not that of LE rats, in the forced swim test, suggesting that blockade of the OCT3 has antidepressant-like effects. Since WKY rats also appear to be resistant to the behavioral effects of traditional antidepressants, this also suggests that OCT3 antagonism may be an alternative therapeutic strategy for the treatment of depression in individuals who do not respond to conventional antidepressants.
Details
- Title: Subtitle
- Modulation of OCT3 expression by stress, and antidepressant-like activity of decynium-22 in an animal model of depression
- Creators
- C A Marcinkiewcz - University of Florida, Department of Neuroscience, McKnight Brain Institute, Gainesville, FL 32610-0015, USAD P Devine - University of Florida, Department of Neuroscience, McKnight Brain Institute, Gainesville, FL 32610-0015, USA; University of Florida, Department of Psychology, Behavioral and Cognitive Neuroscience Program, Gainesville, FL 32611-2250, USA. Electronic address: dpdevine@ufl.edu
- Resource Type
- Journal article
- Publication Details
- Pharmacology, biochemistry and behavior, Vol.131, pp.33-41
- Publisher
- United States
- DOI
- 10.1016/j.pbb.2015.01.004
- PMID
- 25597272
- ISSN
- 0091-3057
- eISSN
- 1873-5177
- Language
- English
- Date published
- 04/2015
- Academic Unit
- Iowa Neuroscience Institute; Neuroscience and Pharmacology
- Record Identifier
- 9984040354002771
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