Effects of a high-dose treatment of methamphetamine on caudate dopamine and anorexia in rats.

Dose-effect curves of d-methamphetamine (MA) on intake of sweetened condensed milk by rats were obtained before and after twice a day treatment for four days with either saline (control) or a high (50 mg/kg) dose of MA previously shown to decrease the dopamine levels of the caudate. The animals that were more sensitive to MA's anorexic effect during the before-treatment determination were found to be more sensitive to the lethal effects of the high-dose treatment. This treatment produced a six month decrease in brain dopamine but no change in the anorexic effect on milk intake or in the stereotypic behavior elicited by the drug. Subsequently, the daily administration of 2.5 mg/kg of MA, 15 min before presentation of the milk, to both control and treatment groups produced tolerance to the drug's anorexic effect. After 4 to 5 weeks of repeated administration of this dose there was a significant difference between the control group's intake of milk and treatment group's intake as well as body weight. These differences indicate an effect on the treatment upon the formation of tolerance to the anorexic effects of MA.