Acute and chronic amphetamine treatment: differential modification of exploratory behavior in a radial maze

Mice permitted to explore an 8-arm radial maze displayed high levels of spontaneous alternation as measured by the frequency of visiting (a) the 4 least recently entered arms, (b) the 2 least recently visited arms, and (c) sequences of arms which are adjacent to one another. Acute treatment with low doses of amphetamine (1.0 mg/kg) eliminated the alternation tendency. Higher doses (5.0-7.0 mg/kg) also produced marked stimulus perseverance, such that mice tended to revisit the two arms that had been most recently entered. With repeated amphetamine treatment the perseverance tendency was attenuated. The abatement of perseverance in the radial maze did not appear to reflect simply the reduction in the potency of the drug. That is, the reduction of perseverance after chronic exposure to amphetamine was not accompanied by recovery of normal exploratory patterns. In fact, the alternation and adjacent alternation patterns typical of naive animals were absent in mice chronically treated with amphetamine even when tested in the nondrug state. It was suggested that the attenuation of amphetamine induced perseverance after chronic amphetamine administration may reflect a breakdown of normal behavior patterns rather than the development of a genuine tolerance.