5-HT1A Serotonergic, alpha-Adrenergic and Opioidergic Receptors Mediate the Analgesic Efficacy of Vortioxetine in Mice

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MOLECULES, vol.26, no.11, 2021 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 26 Issue: 11
  • Publication Date: 2021
  • Doi Number: 10.3390/molecules26113242
  • Journal Name: MOLECULES
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aerospace Database, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, Communication Abstracts, EMBASE, Food Science & Technology Abstracts, MEDLINE, Metadex, Veterinary Science Database, Directory of Open Access Journals, Civil Engineering Abstracts
  • Keywords: vortioxetine, hot-plate test, tail-clip test, tail-immersion test, monoamines, opioid, LU AA21004, MULTIMODAL ANTIDEPRESSANT, SUBSTANTIA-GELATINOSA, ANIMAL-MODELS, DORSAL-HORN, PAIN, ANTINOCICEPTION, INVOLVEMENT, TRANSMISSION, MECHANISMS
  • Anadolu University Affiliated: Yes


Vortioxetine is a multimodal antidepressant drug that affects several brain neurochemicals and has the potential to induce various pharmacological effects on the central nervous system. Therefore, we investigated the centrally mediated analgesic efficacy of this drug and the mechanisms underlying this effect. Analgesic activity of vortioxetine (5, 10 and 20 mg/kg, p.o.) was examined by tail-clip, tail-immersion and hot-plate tests. Motor performance of animals was evaluated using Rota-rod device. Time course measurements (30-180 min) showed that vortioxetine (10 and 20 mg/kg) administrations significantly increased the response latency, percent maximum possible effect and area under the curve values in all of the nociceptive tests. These data pointed out the analgesic effect of vortioxetine on central pathways carrying acute thermal and mechanical nociceptive stimuli. Vortioxetine did not alter the motor coordination of mice indicating that the analgesic activity of this drug was specific. In mechanistic studies, pre-treatments with p-chlorophenylalanine (serotonin-synthesis inhibitor), NAN-190 (serotonin 5-HT1A receptor antagonist), alpha-methyl-para-tyrosine (catecholamine-synthesis inhibitor), phentolamine (non-selective alpha-adrenoceptor blocker), and naloxone (non-selective opioid receptor blocker) antagonised the vortioxetine-induced analgesia. Obtained findings indicated that vortioxetine-induced analgesia is mediated by 5-HT1A serotonergic, alpha-adrenergic and opioidergic receptors, and contributions of central serotonergic and catecholaminergic neurotransmissions are critical for this effect.