Memory and psychostimulants: modulation of Pavlovian fear conditioning by amphetamine in C57BL/6 mice.

RATIONALE AND OBJECTIVES: With the use of prescription stimulants on the rise, it is important to examine the cognitive effects of low and moderate doses of stimulants rather than only those typical of addicts. MATERIALS AND METHODS: The present study examined the effects a range of doses (0.005-8 mg/kg) of D: -amphetamine sulfate on cued and contextual Pavlovian fear conditioning in mice. RESULTS: In agreement with previous research, subjects administered with a moderately high dose of amphetamine (8 mg/kg) pre-training, typical of what addicts might take, displayed impaired conditioned freezing when tested off-drug. Alternately, subjects injected with a very low dose of amphetamine (0.005, 0.025, or 0.05 mg/kg) pre-training, similar to the therapeutic doses for attention deficit hyperactivity disorder, displayed enhanced memory when tested off-drug. A control study showed that these effects were not due to state-dependent learning. CONCLUSIONS: Thus, dose is a critical determinant of the cognitive effects of psychostimulants.