Amphetamine withdrawal: effects on threshold of intracranial reinforcement.

In order to determine whether alterations in sensitivity to rewarding stimuli accompany the biochemical and behavioral changes induced by chronic amphetamine treatment and withdrawal, we explored the effects of chronic administration and withdrawal of d-amphetamine on thresholds of intracranial reinforcement in the rat. Rats were injected with d-amphetamine sulfate according to a chronic, escalating dose schedule. Marked decreases in threshold of intracranial reinforcement were observed immediately (0--1 h) following the last injection of d-amphetamine. In contrast, all animals showed marked increases in thresholds of intracranial reinforcement 24-48 h after the last injection of d-amphetamine. These findings were discussed in relation to amphetamine-induced and naturally occurring depressions in man.