mu- and kappa-Opioids inhibit K+ evoked glutamate release from rat cerebrocortical slices

We have examined the effects of a range of opioid receptor subtype selective agonists on Kt evoked glutamate release from perfused rat cerebrocortical slices. Dual application (S-1 and S-2) of K+ (46 mM) evoked dual monophasic glutamate release profiles. When areas under the release curves were calculated an S-2/S-1 ratio for control slices of 1.07+/-0.08 (n=75) was obtained, this was reduced by 80% with EGTA (0.1 mM) treatment confirming the presence of a Ca2+ regulated release process. Morphine produced a dose-dependent inhibition of the S-2/S-1 ratio. At 1 mu M this amounted to 78+/-12% (mean+/-SEM; n=6). (D-Ala(2),MePhe(4),gly(ol)(5))enkephalin (DAMGO; 60+/-12%, n=6 at 1 mu M), and spiradoline (53+/-14% at 1 and 71+/-11% at 100 mu M, both n=6) also inhibited glutamate release in a cyprodime (10 mu M) and norbinaltorphimine (10 mu M) reversible manner. (D-Pen(2,5))enkephalin (DPDPE; 1 mu M) was ineffective. All agents tested did not affect basal glutamate release. Collectively these data implicate a role for II. and K opioids in the control of evoked glutamate release and their potential for neuroprotective therapy.