Administration of Orexin-A into the Rat Thalamic Paraventricular Nucleus Enhances the Naloxone Induced Morphine Withdrawal

Drug Res (Stuttg). 2022 Apr;72(4):209-214. doi: 10.1055/a-1744-5868. Epub 2022 Apr 6.

Abstract

Objective: Orexin neuropeptides are implicated in physical dependence on opioids and expression of withdrawal symptoms in drug abuse. The paraventricular nucleus of the midline thalamus (PVT) has a high expression of orexin receptors. The current research studied the effect of orexin-A in the PVT area on the development of behavioral indices produced by morphine withdrawal in rats.

Methods: Male Wistar rats weighing 250-300 gr were utilised. To produce drug dependence, morphine (6, 16, 26, 36, 46, 56, and 66 mg/kg, 2 ml/kg) was injected at an interval of 24 hrs for 7 days. To assess the involvement of the orexin in withdrawal syndrome, we injected orexin-A (100 μM, 200 nl) into the PVT for 7 days before each morphine injection. On the day after the last injection of morphine, naloxone (2.5 mg/kg, i.p.) was injected to elicit the morphine withdrawal symptoms which were observed and checked for 25 min.

Results: The results of the current research showed that the orexin-A in PVT enhances the severity of behavioral symptoms prompted by the injection of naloxone in drug-dependent rats.

Conclusions: These observations imply that targeting the orexin receptors in PVT might exhibit a new therapeutic strategy for the future treatment of dependence.

MeSH terms

  • Animals
  • Male
  • Morphine / adverse effects
  • Morphine Dependence* / drug therapy
  • Naloxone / pharmacology
  • Orexin Receptor Antagonists / pharmacology
  • Orexin Receptor Antagonists / therapeutic use
  • Orexin Receptors / metabolism
  • Orexins / metabolism
  • Orexins / therapeutic use
  • Paraventricular Hypothalamic Nucleus / metabolism
  • Rats
  • Rats, Wistar
  • Substance Withdrawal Syndrome* / drug therapy
  • Substance Withdrawal Syndrome* / metabolism

Substances

  • Orexin Receptor Antagonists
  • Orexin Receptors
  • Orexins
  • Naloxone
  • Morphine