Selective modulation of excitatory transmission by mu-opioid receptor activation in rat supraoptic neurons

Opioid peptides profound inhibitory effects on the production of oxytocin a nd vasopressin, but their direct effects on magnocellular neuroendocrine ne urons appear to be relatively weak. We tested whether a presynaptic mechani sm is involved in this inhibition. The effects of mu-opioid receptor agonis t D-Ala(2), N-CH3-Phe(4), Gly(5)-ol-enkephalin (DAGO) on excitatory and inh ibitory transmission were studied in supraoptic nucleus (SON) neurons from rat hypothalamic slices using whole cell recording. DAGO reduced the amplit ude of evoked glutamatergic excitatory postsynaptic currents (EPSCs) in a d ose-dependent manner. In the presence of tetrodotoxin (TTX) to block spike activity, DAGO also reduced the frequency of spontaneous miniature EPSCs wi thout altering their amplitude distribution, rising time, or decaying time constant. The above effects of DAGO were reversed by wash out, or by additi on of opioid receptor antagonist naloxone or selective mu-antagonist Cys(2) -Tyr(3)-Orn(5)-Pen(7)-NH2 (CTOP). In contrast, DAGO had no significant effe ct on the evoked and spontaneous miniature GABAergic inhibitory postsynapti c currents (IPSCs) in most SON neurons. A direct membrane hyperpolarization of SON neurons was not detected in the presence of DAGO. These results ind icate that mu-opioid receptor activation selectively inhibits excitatory ac tivity in SON neurons via a presynaptic mechanism.