Neuropsychotoxicity of Abused Drugs: Molecular and Neural Mechanisms of Neuropsychotoxicity Induced by Methamphetamine, 3,4-Methylenedioxymethamphetamine (Ecstasy), and 5-Methoxy-N,N-diisopropyltryptamine (Foxy)

Abstract

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-methylenedioxymethanphetamine (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.

Distinct Neurochemical Adaptations Within the Nucleus Accumbens Produced by a History of Self-Administered vs Non-Contingently Administered Intravenous Methamphetamine

“…Such data support an active role for methamphetamine-induced glutamate sensitization in regulating at least certain forms of methamphetamine-induced behavioral plasticity, which, based on a rapidly growing body of literature derived from both human and animal studies (eg, Nakagawa and Kaneko, 2008;Vanderschuren and Kalivas, 2000;Wolf, 1998), may extend to methamphetamine-taking and/or -seeking behavior.…”

Alterations in tryptophan and purine metabolism in cocaine addiction: a metabolomic study

“…Interestingly, aberrant degradation in the serotonin pathway leading to increase in n-methylserotonin and its metabolite bufotenine, compounds with psychotomimetic properties, has been implicated in psychiatric disorders (McBride 2000;Takeda et al 1995). Methylation of tryptamine has been important in the development of designer drugs with hallucinogenic and potentially neurotoxic effects such as N,N-dimethyltryptamine (DMT), 5-methoxy-N,N-diisopropyltryptamine ("foxy"), and N-methyltryptamine (Nakagawa and Kaneko 2008). Cocaine exposure has been also found to alter arylalkylamine N-acetyltransferase expression leading to changes in synthesis of acetyl serotonin and melatonin, metabolites that may play a role in behavioral sensitization to cocaine (Akhisaroglu et al 2004;Uz et al 2005).…”

Colorimetric detection and chromatographic analyses of designer drugs in biological materials: a comprehensive review

“…9), have been shown to act as blocker-type inhibitors of SERT-mediated uptake and to have no effect on 5-HT release. Chronic treatments with 5-MeO-DIPT produced serotonergic neurotoxicity [22][23][24][25].…”

“…The word ''entactogen'' was first used by Nichols [21], and the unusual entactogenic effects of MDMA have been hypothesized to be, at least partly, the result of indirect oxytocin secretion via activation of the serotonergic system [21]. Neuropharmacological and electrophysiological data strongly suggest the existence of postsynaptic receptors for tryptamine distinct from those for 5-HT [22][23][24][25]. There may be a rostrally projecting neuronal tryptamine-containing system arising from cell bodies in or near the median raphe nucleus.…”