Opioid actions are initiated at membrane receptors which couple to cel
lular effecters through G protein-mediated pathways, In the central ne
rvous system opioids reduce neuronal activity through the inhibition o
f voltage-dependent Ca2+ channels, the activation of K+ channels and t
he inhibition of adenylyl cyclase. A significant clinical limitation t
o opioid therapy is the development of tolerance, a biological event t
hat has been linked to agonist effects at the receptor level. Molecula
r studies on the consequences of opioid receptor regulation will provi
de a better understanding of the cellular mechanisms involved in the a
gonist-mediated events in tolerance development.