An activity indicator of acute withdrawal depends on amphetamine dose in rats

A moderate dose of amphetamine (AMPH) produces hypoactivity around 20 h post-administration. This hypoactivity may be an indicator of an acute withdrawal state. The purpose was to see how AMPH doses affected the expression of this hypoactivity and, by inference, AMPH-induced acute withdrawal. Rats were housed in individual open fields, with free access to food and water. Light–dark cycles were scheduled such that drug-elicited patterns could be readily detected. Animals first received a series of eight control treatments, and then a series of 10 experimental treatments spaced at 33-h intervals. Different experimental treatment groups received saline, 1.0 mg/kg, 2.0 mg/kg, or 4.0 mg/kg AMPH. The effects of these treatments on 33-h patterns of locomotor activity were observed. Control treatments produced no systematic time-dependent changes in activity beyond the first hour post-treatment. All doses of AMPH produced typical short-term effects: They markedly increased locomotion and/or stereotypy during the first 3 to 6 h post-treatment. Acute and chronic administrations of the 2.0 and 4.0 mg/kg doses also produced similar changes in longer term activity patterns: They produced hypoactivity 20 h later, followed by a recovery of activity around hour 25 post-treatment. The timing of amphetamine-induced hypoactivity and acute withdrawal may be independent of dose over a wide range of doses. Time-dependent changes in AMPH-induced state may influence motivation and drug-related assessments. The methodology described here may provide an easy and rapid way to investigate the determinants of AMPH-induced hypoactivity and acute withdrawal.