Effects of chronic intermittent and continuous amphetamine administration on acoustic startle.

Acoustic startle was evaluated after mice were exposed to two different schedules of long-term amphetamine treatment. Under one schedule, mice received two daily subcutaneous injections of d-amphetamine for 7 consecutive days, whereas the other consisted of continuous administration of amphetamine via a subcutaneously implanted minipump. The enhanced acoustic startle observed after a test dose of d-amphetamine (3.0 mg/kg) was further facilitated when animals were exposed to long-term intermittent amphetamine administration. In contrast, the enhanced startle response to amphetamine was attenuated when mice received chronic continuous exposure to amphetamine. Possible behavioral and neurochemical mechanisms that may be involved in the development of tolerance after continuous amphetamine administration, and reverse tolerance after intermittent amphetamine treatment were discussed.