Thienorphine is a new nonselective partial agonist of
opioid receptors, which is currently under a Phase II clinical trial in China as a new treatment for
opioid dependence. In this study, we compared the effect of
thienorphine with
morphine on long-term potentiation (LTP) in the lateral perforant path (LPP)-granule cell synapse of the rat dentate gyrus (DG). Furthermore, the effect of
thienorphine on the synaptic structure of the CA1 hippocampal region and the expression of
synaptophysin was investigated. Results indicated interesting differences between
thienorphine and
morphine on the modulation of hippocampal synaptic plasticity. Chronic
thienorphine treatment facilitated LTP in the LPP-DG cell synapses more than chronic
morphine treatment. Morphometric measurement and analysis showed that chronic
thienorphine administration decreased the length of the active zone and reduced the thickness of CA1 postsynaptic densities compared with the saline group (control), but were elevated compared with the
morphine group. Furthermore, the expression of hippocampal
synaptophysin was increased with chronic
thienorphine administration but reduced with chronic
morphine treatment. Taken together, our study clearly demonstrates that chronic
thienorphine treatment enhances LTP, modulates hippocampal synaptic structure, and increases the expression of hippocampal
synaptophysin. Therefore, further study is warranted to investigate
thienorphine as a new treatment for
opioid dependence.