[Modification of stereotypy-producing and ambulation-increasing effects following repeated administration of...

Effects of repeated administration of methamphetamine (MAP: 1.25, 2.5 and 5 mg/kg, sc) at an interval of 4 days for 10 times on stereotyped behaviors as well as ambulatory activity in adult male rats of Wistar strain were investigated. In the first administration of MAP 1.25 mg/kg, marked ambulation-increasing effect was observed mixing with simple stereotyped behaviors such as sniffing and head-bobbing. The stereotypy-producing effect of MAP was apparently observed in a dose-dependent manner, and complicated stereotyped behaviors such as head-weaving and licking simultaneously with sniffing and head-bobbing were frequently demonstrated when 5 mg/kg of MAP was first administered. Furthermore, the ambulation-increasing effect after the drug showed biphasic pattern, i.e. pre-stereotypic and post-stereotypic increases in ambulatory activity, because the activity was interfered by the stereotyped behaviors. When MAP was administered repeatedly, the sniffing- and head-bobbing-producing effects were selectively enhanced at any dose, showing sensitization phenomenon (reverse tolerance), and the pre-stereotypic increase in ambulatory activity was inhibited, while the post-stereotypic increase was progressively enhanced. Although the sensitized stereotypy-producing effect was observed more markedly in the 10th administration of MAP 2.5 mg/kg than that in the first administration of MAP 5 mg/kg, the complicated stereotyped behaviors were hardly seen. It is suggested that the sensitization effects are not always identical qualitatively with the effects observed after increase in MAP-dose.