Anti-nociceptive effects of low dose ketamine in mice may be mediated by the serotonergic systems

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dc.authorid0000-0003-2836-2452en_US
dc.contributor.authorErdinç, Meral Alper
dc.contributor.authorUyar, Emre
dc.contributor.authorKelle, İlker
dc.contributor.authorAkkoç, Hasan
dc.date.accessioned2021-11-02T10:24:02Z
dc.date.available2021-11-02T10:24:02Z
dc.date.issued2019en_US
dc.departmentDicle Üniversitesi, Tıp Fakültesi, Dahili Tıp Bilimleri Bölümü, Tıbbi Farmakoloji Ana Bilim Dalıen_US
dc.description.abstractOBJECTIVE: In pain management, alternative medications are necessary due to the development of tolerance to traditional opioid analgesics. Literature data suggest that N-methyl-D-aspartate (NMDA) receptor antagonizing drugs can induce antinociception, and can reduce the opioid requirement. Ketamine is a non-competitive NMDA receptor antagonist drug and has well-known antinociceptive properties. The drug acts not only on NMDA receptors but also has effects on the monoaminergic system and non-NMDA glutamatergic receptors which have vital roles in the regulation of pain. This study was conducted to investigate the serotonergic and glutamatergic involvement in low-dose ketamine (20 mg/kg) analgesia in mice. METHOD: The effects of serotonin were suppressed with two different ways; either the serotonin was depleted with p-chlorophenylalanine (pCPA, 150 mg/kg/d; 4 days) or the serotonin receptors were blocked with methiothepin (0.1 mg/kg), and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors were antagonized with GYKI-52466 (20 mg/kg). Fluoxetine (20 mg/kg; 7 days) was used to increase the serotoninergic activity. We used a hotplate (HP) test to measure pain reaction latencies. Furthermore, we tested sustained analgesic effects of ketamine for six consecutive times (1-hour break between each test). RESULTS: In our experiment, ketamine treatment increased pain reaction latencies, yet it failed to increase the latencies when combined with antiserotonergic drugs, e.g. pCPA and methiothepin. The latencies were increased with AMPA receptor blockade, yet ketamine did not increase the analgesic effect of the AMPA receptor antagonist, i.e. GYKI-52466. In consecutive tests, ketamine was effective for 5 h, and the peak effect was seen at the 3rd-hour test. CONCLUSION: Our data suggest that the activity of the serotonergic system and AMPA receptors are necessary for ketamine to produce antinociceptive effects. In pain management, ketamine can offer an alternative option to traditional analgesics and may be useful to reduce opioid tolerance.en_US
dc.identifier.citationErdinç, M. A., Uyar, E., Kelle, İ. ve Akkoç, H. (2019). Anti-nociceptive effects of low dose ketamine in mice may be mediated by the serotonergic systems. Psychiatry and Clinical Psychopharmacology, 29(3), 252-256.en_US
dc.identifier.doi10.1080/24750573.2019.1605665
dc.identifier.endpage256en_US
dc.identifier.issn2475-0573
dc.identifier.issue3en_US
dc.identifier.scopus2-s2.0-85067058038
dc.identifier.scopusqualityQ4
dc.identifier.startpage252en_US
dc.identifier.urihttps://www.tandfonline.com/doi/full/10.1080/24750573.2019.1605665
dc.identifier.urihttps://hdl.handle.net/11468/8095
dc.identifier.volume29en_US
dc.identifier.wosWOS:000472285700001
dc.identifier.wosqualityQ4
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.institutionauthorErdinç, Meral Alper
dc.institutionauthorKelle, İlker
dc.institutionauthorAkkoç, Hasan
dc.language.isoenen_US
dc.publisherTaylor and Francis Ltd.en_US
dc.relation.ispartofPsychiatry and Clinical Psychopharmacology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectAntinociceptionen_US
dc.subjectGlutamatergic systemen_US
dc.subjectKetamineen_US
dc.subjectOpioid toleranceen_US
dc.subjectSerotonergic systemen_US
dc.titleAnti-nociceptive effects of low dose ketamine in mice may be mediated by the serotonergic systemsen_US
dc.titleAnti-nociceptive effects of low dose ketamine in mice may be mediated by the serotonergic systems
dc.typeArticleen_US

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