Differential interactions of desipramine with amphetamine and methamphetamine: evidence that amphetamine releases dopamine from noradrenergic neurons in the medial prefrontal cortex

Abstract

Amphetamine is more effective than methamphetamine at raising dopamine levels in the prefrontal cortex. The current study tested the hypothesis that norepinephrine transporters are involved in this difference. Using microdialysis, dopamine, norepinephrine, and serotonin were measured in the rat prefrontal cortex after administration of methamphetamine or amphetamine, with and without perfusion of desipramine. Amphetamine raised norepinephrine levels more than methamphetamine did. Desipramine raised dopamine and serotonin levels but did not alter metabolite levels. Desipramine attenuated the increase in dopamine by amphetamine while increasing the dopamine released by methamphetamine. These data suggest that methamphetamine and amphetamine differ in altering prefrontal cortical dopamine levels and in interacting with norepinephrine transporters. It is proposed that amphetamine releases dopamine in the prefrontal cortex primarily through norepinephrine transporters, whereas methamphetamine interacts minimally with norepinephrine transporters.