Attenuation of perseverative behavior after repeated amphetamine treatment: Tolerance or attentional deficits?

Abstract

When permitted to explore an 8-arm radial maze, animals exhibited a systematic pattern of exploration characterized by preference for the most novel arms (spontaneous alternation) and entry into immediately adjacent arms (adjacent alternation). Acute treatment with moderate dosages of amphetamine reduced the proportion of both types of alternation responses and induced marked stimulus perseveration, i.e., consecutive entries between pairs of arms. Prior exposure to the apparatus enhanced the degree of perseveration ordinarily observed, and provoked perseveration after low doses of the drug. In contrast to acute drug treatment, perseveration was reduced after chronic amphetamine administration. However, chronic amphetamine treatment did not appear simply to reduce the potency of the drug. In contrast to the effects of apparatus pre-exposure on the degree of perseveration induced by acute amphetamine treatment, the degree of perseveration was not enhanced by pre-exposure to the maze in mice with a history of chronic amphetamine administration. Moreover, the exploratory pattern evident in chronically treated animals differed from that of control animals even when tested in the nondrug state. That is, animals chronically treated with amphetamine and tested with saline exhibited alternation scores which did not deviate from chance. These data suggest that chronic amphetamine treatment alters the way in which organisms attend, or respond, to environmental stimuli.