Behavioural tolerance to amphetamine and other psychostimulants: the case for considering behavioural mechanisms.

An hypothesis is presented about the nature of behavioural tolerance in animals to stimulant drugs. It is suggested that, in many behavioural procedures, tolerance is due to behavioural adaptation to those drug effects which cause disruption of ongoing rewarded behaviour. This unitary hypothesis accounts for the available data on tolerance and cross-tolerance to stimulants more effectively than all of the other more conventional explanations which are based upon dispositional or functional concepts, the most common of which are described, evaluated, and found to be inadequate. Furthermore, it is suggested that attempts to explain tolerance in terms of changes in synaptic functioning are subject to very considerable problems of interpretation and that an analysis of behavioural mechanisms may be of greater value in understanding the process of behavioural tolerance. Evidence for the basic behavioural hypothesis is outlined in some detail, and a theoretical justification presented for its major assumptions. Operant studies of chronic stimulant effects on behaviour have often produced very complex patterns of data, considerable differences being reported both between subjects and between studies. A speculative model is presented which attempts to account for this pattern of data in tolerance studies.