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

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.

Orexin-1 Receptor Antagonist SB-334867 Enhances Formalin-Induced Nociceptive Behaviors in Adult Male Rats

“…It has been shown that orexin-A displays analgesic effects analogous to morphine as measured via the hot-plate test. Some evidence displayed that the blockade of OXR1 reduced physical dependence in rats 9 – 11 . Numerous researches have discovered that orexinergic neurons and receptors are expressed at different levels of the descending pain modulation system 12 , 13 .…”