Catecholamines and drug-behavior interactions

The effects of several drugs on schedule-controlled operant behavior depend on the baseline rate of responding and on the nature of the environmental conditions that maintain the behavior. For example, the effects of amphetamine and alpha-methylpara-tyrosine (alphaMT) on operant performances depend to a large extent on the rate at which organisms respond under nondrug control conditions. A neurochemical mechanism for these rate-dependent effects has not been established. However, several lines of evidence suggest that catecholamines are functionally important in the maintenance of many types of behavior, including operant behavior. The fact that many drugs which exhibit drug-behavior interactions also produce characteristic effects on the metabolism of central nervous system catecholamines suggests that the performance of operant behavior per se modifies brain catecholamine metabolism and thereby the subsequent drug effect. Experiments measuring the depletion of catecholamines following synthesis inhibition with alphaMT, or changes in the specific activity of norepinephrine after tritium labeling, have shown that operant behavior alters the metabolism of catecholamines. Preliminary evidence is also presented from experiments designed to determine variables associated with the performance-induced changes in catecholamine metabolism. These variables include: rate of responses; rate or density of reinforcement; and response-reinforcer contingencies. The results of these experiments suggest a neurochemical mechanism for the rate-dependent effects of amphetamine and alphaMT. A model is presented that may account for the general phenomenon of drug-behavior interactions in neurochemical terms.