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The effects of repeated (5 times) subcutaneous administration of cocaine (10, 20 or 40 mg kg-1) and methamphetamine (1, 2 or 4 mg kg-1) at 3-4 day intervals have been compared in mice placed individually into tilting activity cages. A progressive enhancement of the ambulation-increasing effect was noted for 3-4 h after each administration, indicating that sensitization occurred. This occurrence and the existence of an optimal dose producing sensitization were similar for both drugs. However, enhancement of the effect after cocaine progressed rapidly and maximum sensitization was observed earlier than after methamphetamine administration. Moreover, the higher doses of cocaine (40 mg kg-1) caused stereotypies concurrent with preconvulsive signs of short duration that were enhanced by serial administration. In contrast, methamphetamine caused a more progressive enhancement, but stereotypies with no preconvulsive signs were produced by the higher dose (4 mg kg-1). The respectively, effective doses for the development of enhancement suggested that cocaine was less potent than methamphetamine in producing sensitization. Cross-sensitization occurred between both drugs. Thus, sensitization to cocaine was distinct from that to methamphetamine due to differences in its rapidity, intensity, and the presence or absence of preconvulsive changes.

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The development of sensitization to the ambulation-increasing effect of (+)-amphetamine (2.5 mg kg-1) was found to be dose-dependently inhibited when 1 or 2 mg kg-1 chlorpromazine was administered concomitantly, and the sensitization to (+)-amphetamine was almost completely suppressed when co-administered with 4 mg kg-1 chlorpromazine. Following a challenge dose of 2.5 mg kg-1 (+)-amphetamine, mice pretreated with (+)-amphetamine alone or with (+)-amphetamine plus 1 or 2 mg kg-1 chlorpromazine showed similar marked enhancement of the sensitization. However, mice that had been given (+)-amphetamine plus 4 mg kg-1 chlorpromazine displayed only slight enhancement of the effect compared with the activity level in saline-pretreated mice.