Amphetamine stereotypy, the basal ganglia, and the "selection problem"

Abstract

Amphetamine and other stimulant drugs induce stereotyped head movements in rats, which interfere with normal goal-directed behavior. However, rats given access to food while intoxicated learn to suppress these movements in order to feed. This suggests that the suppression of stereotypy is an instrumentally learned response reinforced by the ingestion of food. Consistent with this interpretation, rats learn to suppress stereotyped head movements when intraoral infusions of milk are made contingent on maintaining a stationary head position, but not when such infusions are given noncontingently. Although learning to suppress stereotypy occurs at different rates across subjects, the temporal dynamics of learning are similar in all cases. Moreover, once learned suppression is acquired, it is generally retained over long periods of time unless the contingency between suppression and reinforcement is degraded. Conceptually, the behavioral conflict between drug-induced stereotyped movements and feeding may be viewed as a special case of the "selection problem," which arises whenever organisms are confronted with competing behavioral opportunities. Interestingly, both normal response selection and stimulant-induced stereotypy are associated with overlapping cortico-basal ganglia circuits. Preliminary findings suggest that the learned suppression of stereotypy involves the activation of particular structures within the dorsal and ventral striatal output pathways. Understanding the neural mechanisms underlying the learned suppression of stimulant-induced stereotypy may provide new insights into the process by which the nervous system solves the selection problem and lead to the development of more effective treatments for disorders characterized by insufficient response inhibition, such as Tourette's syndrome and stimulant drug addiction.