Expression of the nociceptin receptor during zebrafish development: influence of morphine and nociceptin

The NOP system is considered to be part of the opioid system, although it exerts antiopioid actions depending on the anatomical region where it is localized. This apparent controversy has lead to the hypothesis that the NOP system interacts with the classical opioid systems (mu, delta, kappa) and regulates/modulates their activity in relation to analgesia and the development of addiction to drugs. In order to shed light into the importance of the NOP system, we have analyzed the expression of NOP during zebrafish development, and the effect of its endogenous agonist nociceptin and the opioid agonist morphine on NOP expression. Our qPCR study show that the number of NOP transcripts is different at each developmental stage studied (0.5 hpf, 2.75 hpf, 3 hpf, 8 hpf, 16 hpf, 19 hpf, 22 hpf, 24 hpf, 30 hpf, 48 hpf, 60 hpf and 72 hpf). Nociceptin enhances NOP expression at 24 hpf but decreases the number of NOP copies at 48 hpf, whereas NOP expression decreases after morphine exposure at 24 hpf and 48 hpf. Also, our ISH analysis demonstrates that nociceptin causes a change in the distribution of NOP towards rostral areas at both developmental stages. Morphine produces similar changes to those of nociceptin although only at 48 hpf. The present work leads to the conclusion that the NOP system is important during embryogenesis. Exposure to drugs changes the expression level and localization of NOP, suggesting that also during development, NOP plays a role in the apparition of dependence and addiction to drugs.