Effects of intermittent and repeated administration of d-amphetamine on restricted water intake in rats

Eleven rats had access to water 2 hours daily and intake was measured every 20 minutes. When given intermittently, increasing doses of d-amphetamine (0.05-1.6 mg/rat) decreased total water intake and altered the within-session distribution of intake, with proportionately less intake occurring within early portions of the session after larger doses. Repeated administration of d-amphetamine (0.2, 0.8 or 1.6 mg/rat/day) completely attenuated the overall intake-decreasing effects of the drug; the time taken for recovery of total intake increased with increasing dose. Despite complete tolerance to its overall intake-decreasing effects, d-amphetamine produced persistent dose-related effects on the distribution of intake within sessions that were only partially attenuated with continued daily administration of the drug. Tolerance to the overall intake-decreasing effect of 1.6 mg was accompanied by parallel shifts toward larger doses in the dose-effect functions for total water intake and for the within-session distribution of intake. Redetermination of the dose-effect functions at several times after the repeated administration of 1.6 mg generally showed that tolerance of d-amphetamine was lost within 25 to 57 days after discontinuation of the drug.