Behavioral assessment of high-dose amphetamine withdrawal: Importance of training and testing conditions

Chronic d-amphetamine-treated rats were given twice daily injections at a dose of 7.5 mg/kg for 2 weeks. Acute amphetamine and saline groups of rats were given saline treatments during this time, except that for the acute group the final injection was 7.5 mg/kg d-amphetamine. Acute and chronic amphetamine groups habituated to the locomotor activity testing apparatus showed increases in both distance traveled and repetitive movement time that lasted up to 6 h following the final injection. When animals were not habituated to the activity test apparatus, however, a significant decrease in repetitive movement time was noted for the chronic amphetamine group 24-54 h following the final amphetamine injection; no differences were observed for distance traveled when the locomotor activity apparatus was novel. Swim test immobility time was assessed twice following the last injection, with the second test following the first by approximately 24 h. During the first test, decreases in immobility were observed for both chronic and acute amphetamine groups, 6-12 h following the last injection. However, during the second test, decreases in immobility time were observed only for the chronic amphetamine groups 36-72 h following the final injection. These results indicate that 24 to 72 h after the end of the chronic amphetamine regimen a withdrawal effect was observed for both repetitive movement time in the locomotor activity test and immobility time in the swim test. The withdrawal effect was observed only for the locomotor activity groups for whom the test apparatus was novel, and only during the second test of immobility time for the swim test groups. Thus, the method of behavioral assessment can be critical for the demonstration of a high-dose amphetamine withdrawal effect.