The role of the aversive effects of drugs in self-administration: assessing the balance of reward and aversion in drug-taking behavior.

Since the first experimental demonstration that a drug of abuse supports instrumental behavior, drugs have been discussed in the context of their rewarding effects, which are assumed to drive and maintain drug-taking behavior. Indeed, drug reward has been fundamental in the formulation of most models of drug use, abuse, and addiction. Over the last several decades, however, drugs of abuse have been increasingly recognized as complex pharmacological compounds producing multiple stimulus effects, not all of which are rewarding. The aversive effects of such drugs, for example, have been described by a number of researchers working in the field, although few attempts have been made to investigate the role of these aversive effects in drug taking. The present paper offers a historical perspective on the view that drugs of abuse are complex pharmacological compounds with multiple stimulus effects. In doing so, we argue that the discussion of drug reward only may be insufficient in accounting for drug taking and we present evidence for the theoretical position that both the rewarding and the aversive effects of drugs should be taken into consideration in ongoing attempts to model drug-taking behavior. The present review summarizes several decades of research characterizing the aversive effects of major drugs of abuse, as well as more recent studies seeking to assess directly the role of drug aversion in drug taking.