Tolerance to d-amphetamine: Behavioral specificity
In a Y-maze exploratory task mice tend to enter that compartment which was least recently visited (spontaneous alternation). Low doses of d-amphetamine (1.0 mg/kg) reduce alternation to chance levels, while high doses (10.0 mg/kg) result in animals successively visiting only two compartments of the Y-maze (perseveration). Following daily d-amphetamine injection (1.0 or 10.0 mg/kg) over a 30 day period tolerance to the d-amphetamine induced perseveration was observed; however, chronic amphetamine treatment did not modify the locomotor stimulating effects of d-amphetamine or the reduction of alternation to chance levels produced by low doses of the drug. It was hypothesized that tolerance to d-amphetamine occurs exclusively to behaviors mediated by norepinephrine.
Kokkinidis, L. (Larry), Walsh, M.D. (Michael D.), Lahue, R. (Robert), & Anisman, H. (1976). Tolerance to d-amphetamine: Behavioral specificity. Life Sciences, 18(9), 913–917. doi:10.1016/0024-3205(76)90408-2