Fundamental mechanisms underlying altered behavior following chronic administration of psychomotor stimulants

Psychomotor stimulant-induced abnormal behavior in man and experimental animals has provided a model for investigation of the biobehavioral basis of psychosis for the past decade. The altered behavior which occurs with chronic administration of psychomotor stimulants appears to be attributable to five major phenomena: One of these, conditioning, involves a global reorganization whose biological bases are little understood. Alterations reflecting kindling mechanisms represent changes in membrane mechanisms resulting in enhanced propagation of electrical signals. A third mechanism involves adaptation of drug metabolism systems, and the final two involve aminergic neuronal function, i.e., decreased levels of dopamine and possibly alterations in other amine systems and increased number of dopamine receptors. Evidence linking behavioral reorganization as a result of chronic administraton of psychomotor stimulants with these phenomena is presented.