ABSTRACT
The phenomenon of opioid tolerance and dependence can be viewed as the spectrum of changes which occur as an organism adjusts to the continuing presence of an opioid drug. Thus, mechanisms come into play at the biochemical and cellular levels, as well as at the level of neuronal systems and behavior, which together promote homeostasis. The considerable research efforts expended to determine the mechanisms responsible for morphine tolerance and dependence have substantially increased our understanding of this important scientific and clinical issue (Smith et al., 1988; Rothman, 1992). These studies have tended to focus on the role which changes in receptors and receptor-coupling mechanisms play in opioid tolerance and dependence (Collier, 1965; Sharma et al, 1975; Chang, Eckel, and Blanchard, 1982; Law, Koehler, and Loh, 1982; Law, Horn, and Loh, 1983; Chavkin and Goldstein, 1984; Terwilliger et al, 1991).
