Enhancement of motor-accelerating effect induced by repeated administration of methamphetamine in mice: involvement of environmental factors.

Adult male mice were given 2.0 mg/kg of methamphetamine hydrochloride (MAM) for 6 times at 3-4 day intervals. The acute effects of MAM on locomotor activity of each mouse were investigated for 180 min after each administration. The motor-accelerating effect of MAM was progressively enhanced in parallel to the number of administrations. However, the enhancement of effect was not observed after repeated administration of MAM, when the mice were placed individually in narrow jars, which thereby perfectly inhibited ambulation during 180 min following each administration. The other mice were trained under the discriminated shuttle-type avoidance schedule (intertrial interval = 25 sec, CS presentation = 6 sec and 1 session = 1 hr). A slight influence of training on locomotor activity was detected after 2.0 mg/kg of MAM in the activity cage. A marked enhancement of the motor-accelerating effect was detected in the avoidance-trained mice, when 2.0 mg/kg of MAM was given for 5 times at 3-4 day intervals in the avoidance situation. These results suggest that the conditioned drug effect in association with environmental factors plays an important role in the production of enhancement.

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