Affiliations 

  • 1 Centre for Drug Research, Universiti Sains Malaysia, 11800, Minden, Penang, Malaysia
  • 2 Institute for Research in Molecular Medicine, Universiti Sains Malaysia, 11800, Minden, Penang, Malaysia
  • 3 Section of Addiction Medicine, Department of Psychiatry and Psychotherapy, University Clinic, Friedrich-Alexander-University Erlangen-Nuremberg, Schwabachanlage 6, 91054, Erlangen, Germany. Electronic address: Christian.Mueller@uk-erlangen.de
  • 4 Centre for Drug Research, Universiti Sains Malaysia, 11800, Minden, Penang, Malaysia; Addiction Behaviour and Neuroplasticity Laboratory, National Neuroscience Institute, 11 Jalan Tan Tock Seng, 308433, Singapore. Electronic address: zurina_hassan@usm.my
Brain Res Bull, 2021 07;172:139-150.
PMID: 33901587 DOI: 10.1016/j.brainresbull.2021.04.018

Abstract

Mitragyna speciosa, also known as kratom, has been used for mitigating the severity of opioid withdrawal in humans. Its main indole alkaloid, mitragynine, has been considered as a pharmacotherapy for pain conditions and opioid replacement therapy. However, at high doses, chronic mitragynine may also have an addiction potential. The effects of chronic action of mitragynine in the brain are still unknown. The present study developed a mitragynine withdrawal model in rats and used it for a proteomic analysis of mitragynine withdrawal effects. Mitragynine (30 mg/kg, i.p.) was administered daily over a period of 14 days and then withdrawn. A proteomic analysis revealed that from a total of 1524 proteins identified, 31 proteins were upregulated, and 3 proteins were downregulated in the mitragynine withdrawal model. The Rab35 protein expression increased most profoundly in the mitragynine withdrawal group as compared to vehicle group. Therefore, it is proposed that Rab35 in the brain might be considered as a potential biomarker during mitragynine withdrawal and might be valuable target protein in developing new pharmacotherapies in the future.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.