Development of acute withdrawal during periodic administration of amphetamine in rats.

Amphetamine (AMPH) administration appears to produce multiple time-dependent effects during the approximately 24-h period after administration. This study examined the development of these effects. Rats were housed in separate cubicles, had ad-lib access to food and water, and were continuously monitored. After a series of control treatments, different groups received AMPH (1.0 mg/kg ip) at either 33- or 24-h intervals. Light-dark cycles (12-12 h) were "staggered" by 3-h intervals across the rats in each group, so that the effects of AMPH could be readily detected in average activity profiles against the background of light-entrainable activity. Changes in activity indicated that AMPH produced a common sequence of effects on both 33- and 24-h-period schedules: psychomotor stimulation (Hours 1-3 postdrug), withdrawal (activity suppression near Hour 20 postdrug), and recovery (activity increase beginning around Hour 24 postdrug). Withdrawal and recovery effects developed during the first several AMPH administration cycles. These time-dependent changes during the approximately 24-h interval after AMPH administration could reflect changes in motivation and in susceptibility to processes thought to underlie the acquisition of drug abuse (such as the positive and negative reinforcing effects of drug receipt). Short- and long-term responsiveness to drug might then depend on when in the postdrug sequence administrations occur.