Morphine dependence increases gene expression of orexin type one receptors in locus coeruleus nucleus

Repetitive administration of opioid agonists induced dependency to these substances and thus limits their clinical usage. The locus coeruleus (LC) is a key brain structure implicated in dependency tolerance and the expression of somatic signs of morphine withdrawal syndrome. Orexin is a neuropeptide that involve in morphine tolerance and dependence, as well. OX1R has been detected in LC nucleus. In this study we examined the expression of OX1R during dependency and also in the withdrawal syndrome in neurons of LC nucleus in rats.

To incite dependency, morphine sulfate (10 mg/kg) was injected intraperitoneally twice a day for 10 days in male Wistar rats. For induction of withdrawal syndrome, naloxone was injected (2 mg/kg) subcutaneously in day 10, two hours after the last injection of morphine. In order to measure the expression of OX1R, RT-PCR was used.

This study shows that morphine dependency leads to increase expression of OX1R in neurons of LC nucleus. We also observed that morphine withdrawal syndrome with naloxone induced decreasing of OX1R expression in this region. In another word, amounts of this receptors back to normal level before dependency.

Due to results obtained from this study, we observed an increase in the expression of OX1R in neurons of LC nucleus and also return in the level of this receptors to baseline after exposure to naloxone and withdrawal syndrome. Hence we could suggest that OX1Rs in LC nucleus are involved in dependency and withdrawal syndrome.