Effects of thienorphine on synaptic structure and synaptophysin expression in the rat nucleus accumbens

• Thienorphine affected synaptic ultra-structure in the NAc of rats.
• Thienorphine increased synaptophysin expression in the NAc of rats.
• Thienorphine is deserved to be studied as a new treatment for opioid dependence.

The partial opioid agonist thienorphine is currently in Phase II clinical trials in China as a candidate drug for the treatment of opioid dependence. However, its effect on synaptic plasticity in the NAc (nucleus accumbens) remains unclear. In the present study, we measured structural parameters of the synaptic interface to investigate the effect of thienorphine, morphine or a combination of both on synaptic morphology in the NAc of rats. Expression of synaptophysin was also examined. Ultrastructural observation showed that synaptic alterations were less pronounced after chronic thienorphine administration than after chronic morphine administration. Animals that received thienorphine had thinner postsynaptic densities and shorter active zones in the NAc compared with those in the saline group, but the active zone was larger, and the cleft narrower, than those in the morphine group. Furthermore, synaptophysin expression in the NAc was significantly greater after chronic administration of thienorphine, morphine, or both, than after saline. These results identified interesting differences between thienorphine and morphine in their effects on synaptic structure and synaptophysin expression in the rat NAc. Further study is deserved to investigate thienorphine as a new treatment for opioid dependence.