MU-OPIOID AND DELTA-OPIOID SYNERGY BETWEEN THE PERIAQUEDUCTAL GRAY AND THE ROSTRO-VENTRAL MEDULLA

Microinjection of [D-Ala(2),MePhe(4),Gly(ol)(5)]enkephalin (DAMGO) into either the periaqueductal gray (PAG) or the rostral ventral medulla (RVM) elicts analgesia in the tailflick assay in the rat. Co-admininstration of DAMGO into both regions together results in a profound synergistic interaction similar to that we previously reported with morphine. U50,488H and DPDPE are inactive when given into either region. [D-Ala(2),Glu(4)]Deltorphin (deltorphin), on the other hand, elicits an analgesic response, although the maximal response is less than than mu agonists. Co-administration of DAMGO into one region with deltorphin in the ether also results in a significant synergy. However, co-administration of DAMGO and deltorphin together in the same region gives only additive effects. These results confirm the existence of mu/mu synergy between the FAG and RVM. kappa 1 and delta 1 agents are inactive, but the delta(2) agonist deltorphin is active in both regions. Our results indicate the presence of mu/delta(2) synergy between the PAG and RVM which appears to involve interactions of pathways rather than receptor interactions at the cellular level.