Reverse tolerance to the swimming time prolonging effect of d-amphetamine in mice

Development and disappearance of reverse tolerance to the swimming time prolonging effect of d-amphetamine (AMP) was studied in mice in comparison with that to the ambulation accelerating effect. The swimming time prolonging effect was progressively enhanced by daily administration of 2 mg/kg AMP. The development of reverse tolerance to the effect was more rapid than that to the ambulation accelerating effect and reached its maximal level by 5-6 repetitions. Repetition at a daily interval was more effective than at the interval of 3-4 days, and administration at a weekly interval failed to develop the reverse tolerance. Restriction of swimming space or immobilization in a small box after administration of AMP blocked the development of reverse tolerance. Reverse tolerance to the swimming time prolonging effect disappeared faster than that to the ambulation accelerating effect, but the enhancement was well maintained after 30 days of withdrawal. Thus, many factors affect the development of reverse tolerance to the various effects of AMP; however, the swimming time prolonging effect is a simple, sensitive, and reproducible index for the study of this phenomenon.