Role of reward and enhancement of conditioned reward in persistence of responding for cocaine.

The primary rewarding effects of cocaine, based presumably on its powerful euphoric properties, are widely recognized and have been implicated as a major factor in the abuse potential of this drug. Several different experimental procedures have been developed to study the rewarding properties of cocaine in animals, and three of the most influential techniques, namely intravenous self-administration, pharmacological enhancement of brain-stimulation reward, and conditioned place preference, are described briefly. A related influence of cocaine that may also contribute to its strong control over behavior is the enhancement of the effects of conditioned rewarding stimuli. Experiments that exemplify this phenomenon are described along with those that relate to its neural substrates. Accordingly, the argument is advanced that the compulsion to abuse cocaine may be based on two distinct effects; (1) primary reward related to euphoria and (2) a more subtle but equally potent influence by which the drug amplifies or enhances the effects of conditioned rewarding stimuli. The final section of the paper reviews the literature pertaining to the facilitation of extinction by neuroleptic drugs. A combined behavioral pharmacologic intervention, involving extinction procedures in conjunction with neuroleptic treatment, is proposed as a potential therapeutic strategy for breaking the cocaine habit in humans.