Neuropsychotoxicity of abused drugs: molecular and neural mechanisms of neuropsychotoxicity induced by methamphetamine, 3,4-methylenedioxymethamphetamine (ecstasy), and 5-methoxy-N,N-diisopropyltryptamine (foxy).

Drugs of abuse such as amphetamines, cocaine, opioids, and recreational drugs cause dependence and addiction by converging on common neural pathways. Chronic treatment enhances mesocorticolimbic dopaminergic neurons from the ventral tegmental area to the nucleus accumbens and medial prefrontal cortex, and disrupts glutamatergic function between these regions. Serotonergic neurons from the raphe nuclei to limbic areas also modulate this system and contribute to neuropsychotoxicity. This review introduces the authors' in vitro studies on methamphetamine, MDMA (ecstasy), and 5-MeO-DiPT (foxy) using Xenopus oocytes and organotypic slice cultures to examine molecular targets and neural adaptation.

Study at a glance

Abstract

Psychostimulants including amphetamines and cocaine, opioids including morphine, and some recreational drugs share the ability to cause drug dependence and addiction. Although these drugs of abuse primarily act on distinct molecular targets, such as monoamine transporters or receptors, they finally converge to common neural pathways. Several lines of evidence suggest that their chronic treatment leads to the enhancement of the mesocorticolimbic dopaminergic neurons from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) and the medial prefrontal cortex (mPFC) and leads to abnormal glutamatergic function from the mPFC to the NAc and VTA. The neural adaptation of dopaminergic-glutamatergic system is considered to be critically implicated in neuropsychotoxic effects of these drugs of abuse. In addition, recent studies suggest that the serotonergic neurons from the raphe nuclei to limbic areas modulate the mesocorticolimbic dopaminergic-glutamatergic system and participate in the neuropsychotoxicity. In this review, our recent in vitro studies on the molecular targets and neural adaptation of methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy"), and 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DiPT, "foxy") using Xenopus oocytes, organotypic slice cultures of the mesocorticolimbic dopaminergic-glutamatergic system, and the raphe serotonergic system are introduced.