Monoamine transporter as a target molecule for psychostimulants.

ABSTRACT

Methamphetamine (MAP), a drug of abuse known worldwide for its addictive effects and neurotoxicity, causes somatic and psychiatric disorders. MAP enters terminals/neurons via monoamine transporters, displaces both vesicular and intracellular monoamines, and facilitates the release of monoamines into the extraneuronal space through synaptic transport via the monoamine transporters. Chronic psychostimulant abusers exhibit psychotic features, including delusions and auditory hallucinations. The dopamine transporter (DAT) and the vesicular monoamine transporter 2 (VMAT2) play pivotal roles in the action of MAP, including locomotor effects. The deletion of DAT attenuates the locomotor effects of MAP and may play larger role in behavioral responses to MAP compared to the deletion of VMAT2. MAP produces hyperthermia and/or neuronal toxicity in most species. The effects of MAP in DAT or serotonin transporter (SERT) single knockout (KO) mice and DAT/SERT double KO mice suggested that DAT and SERT are key molecules for hyperthermia and neuronal toxicity of MAP.