ANALGESIA AND ABUSE POTENTIAL - AN ACCIDENTAL ASSOCIATION OR A COMMONSUBSTRATE

The fact that centrally acting analgesics have abuse potential commens urate with their analgesic activity raises the question of whether the se effects are related. The abuse potential of drugs depends on their ability to produce reinforcing effects, which are mediated by a neural system that includes the ventral tegmental dopamine cells and their c onnections with the ventral striatum. Morphine and amphetamine are bot h powerful analgesics and have high abuse potential. Their analgesic a nd reinforcing effects are mediated by similar receptors, similar site s of action, and overlapping neural substrates. These coincidences sug gest that reinforcers may produce analgesia by transforming the aversi ve affective state evoked by pain into a more positive affective state . The implications of this hypothesis and its relation to other known mechanisms of analgesia are discussed. The hypothesis predicts that dr ugs with reinforcing effects should produce analgesia. A survey of dru gs acting through 21 classes of receptors reveals that in 13 classes t here is evidence for both analgesic and reinforcing effects that are a pproximately equipotent. The GABA(A) agonists were found to be the onl y drugs with confirmed abuse potential that lack analgesic activity. T he interpretation of this and several other anomalous cases is discuss ed. (C) 1998 Elsevier Science Inc.