[Studies on the reverse tolerance phenomenon after repeated methamphetamine treatment in rats]

Male rats of the Wistar strain were divided into three groups, to which three different doses of methamphetamine (MAP), 0.5 mg, 2 mg, and 4 mg/kg/day, respectively, were intraperitoneally administered 5 times per week for 36 days. Stereotyped behaviors were scored according to the method of Ellinwood & Balster. During the period of repeated MAP treatment, these behaviors increased in a dose dependent manner. Group I treated with 0.5 mg/kg of MAP demonstrated more prominently an increased sensitivity to MAP than the other two, Group II with 2 mg/kg and Group III with 4 mg/kg. Following the withdrawal period of 4 weeks, the rats were reinjected with 0.5 mg/kg of MAP. They showed higher scores of stereotypies than those treated acutely with MAP, that is, reverse tolerance for MAP was observed, although this phenomenon was not necessarily observed in a dose dependent manner for each variable of the behaviors. Lethal autonomic response was observed in Group I and II, in which animals appeared to have reverse tolerance for autonomic response to MAP reinjection in contrast to in Group III. It can be concluded that repeated administration of MAP induces stereotyped behaviors in a dose dependent manner, while autonomic response is not likely to form tolerance.