Modulation of OCT3 expression by stress, and antidepressant-like activity of decynium-22 in an animal model of depression
| Autor: | Catherine A. Marcinkiewcz, Darragh P. Devine |
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| Rok vydání: | 2015 |
| Předmět: |
Male
medicine.medical_specialty Clinical Biochemistry Hippocampus Organic Anion Transporters Sodium-Independent Toxicology Rats Inbred WKY Biochemistry Social defeat Behavioral Neuroscience chemistry.chemical_compound Downregulation and upregulation Internal medicine medicine Animals Rats Long-Evans Biological Psychiatry Pharmacology Depression Decynium-22 Antidepressive Agents Pathophysiology Rats Blockade Disease Models Animal Monoamine neurotransmitter Endocrinology chemistry Quinolines Psychology Stress Psychological Clinical psychology Behavioural despair test |
| Zdroj: | Pharmacology Biochemistry and Behavior. 131:33-41 |
| ISSN: | 0091-3057 |
| DOI: | 10.1016/j.pbb.2015.01.004 |
| Popis: | 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 2 h 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 3 h 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 10 μg/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. |
| Databáze: | OpenAIRE |
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