Serotonergic Neurotransmission System Modulator, Vortioxetine, and Dopaminergic D2/D3 Receptor Agonist, Ropinirole, Attenuate Fibromyalgia-Like Symptoms in Mice

Molecules. 2021 Apr 20;26(8):2398. doi: 10.3390/molecules26082398.

Abstract

Fibromyalgia is a disease characterized by lowered pain threshold, mood disorders, and decreased muscular strength. It results from a complex dysfunction of the nervous system and due to unknown etiology, its diagnosis, treatment, and prevention are a serious challenge for contemporary medicine. Impaired serotonergic and dopaminergic neurotransmission are regarded as key factors contributing to fibromyalgia. The present research assessed the effect of serotonergic and dopaminergic system modulators (vortioxetine and ropinirole, respectively) on the pain threshold, depressive-like behavior, anxiety, and motor functions of mice with fibromyalgia-like symptoms induced by subcutaneous reserpine (0.25 mg/kg). By depleting serotonin and dopamine in the mouse brain, reserpine induced symptoms of human fibromyalgia. Intraperitoneal administration of vortioxetine and ropinirole at the dose of 10 mg/kg alleviated tactile allodynia. At 5 and 10 mg/kg ropinirole showed antidepressant-like properties, while vortioxetine had anxiolytic-like properties. None of these drugs influenced muscle strength but reserpine reduced locomotor activity of mice. Concluding, in the mouse model of fibromyalgia vortioxetine and ropinirole markedly reduced pain. These drugs affected emotional processes of mice in a distinct manner. Hence, these two repurposed drugs should be considered as potential drug candidates for fibromyalgia. The selection of a specific drug should depend on patient's key symptoms.

Keywords: mouse; reserpine-induced fibromyalgia model; ropinirole; serotonin and dopamine in fibromyalgia; vortioxetine.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Dopamine / genetics
  • Dopamine Agonists / pharmacology*
  • Fibromyalgia / drug therapy*
  • Fibromyalgia / genetics
  • Fibromyalgia / pathology
  • Humans
  • Indoles / pharmacology*
  • Mice
  • Pain / drug therapy*
  • Pain / genetics
  • Pain / pathology
  • Pain Threshold
  • Receptors, Dopamine D2 / agonists
  • Receptors, Dopamine D3 / agonists
  • Serotonin / genetics
  • Synaptic Transmission / drug effects
  • Vortioxetine / pharmacology*

Substances

  • Dopamine Agonists
  • Indoles
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • ropinirole
  • Serotonin
  • Vortioxetine
  • Dopamine