Modulatory effect of environmental stimuli on the susceptibility to amphetamine sensitization: a dose-effect study in rats.

In previous studies the repeated administration of 0.5 to 1.0 mg/kg of amphetamine i.v. failed to induce psychomotor sensitization if the drug was administered to animals living in the test environment (at home). The same doses did induce sensitization if animals were transported to the test environment for each drug treatment. The purpose of the present experiment was to determine the extent to which this effect of environment is dose dependent. Rats either lived in test cages or were transported from the animal colony to test cages where they received an i.v. infusion of one of five doses of amphetamine (0.125, 0.5, 1.0, 4.0 or 8.0 mg/kg) or saline each day for 5 consecutive days. Rotational behavior was used as an index of psychomotor activation. After a 6-day drug-free period all animals were challenged with 0.5 mg/kg of amphetamine to determine the pretreatment dose necessary to induce sensitization. The effect of the drug-treatment environment was to shift the dose-effect curve for the induction of sensitization, such that significantly lower doses were necessary to induce sensitization when amphetamine was given in a novel environment. With high doses, however, sensitization occurred regardless of environmental condition. It is concluded that the circumstances surrounding drug administration can powerfully modulate the ability of psychostimulants to induce sensitization, but this effect is dose dependent.