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Substances of Abuse and Hallucinogenic Activity: The Glutamatergic Pathway - Focus on Ketamine

  • Gian Mario Mandolini
  • Matteo Lazzaretti
  • Alfredo Carlo Altamura
  • Paolo BrambillaEmail author
Chapter

Abstract

This chapter analyzes the glutamatergic pathway involved in the induction of hallucinations. Indeed, the development of the so-called glutamate hypothesis of psychotic disorders arises from the evidence that glutamate signalling antagonism can induce psychotic symptoms in healthy subjects. Ketamine seems to have the capacity of inducing not only dissociative symptoms, but also psychotic symptoms such as hallucinations. The main molecular mechanism of action of ketamine is due to its glutamate-dependent property. Ketamine also has other glutamate-independent mechanisms of action which include interaction with dopaminergic receptors, as well as with opioid, muscarinic, serotonin, and noradrenaline ones. Ketamine primarily acts as a noncompetitive antagonist of the N-methyl-d-aspartate (NMDA) receptor, leading to an increase in glutamate release in prefrontal cortex. The antagonism on NMDA receptors is thought to cause the dissociative effect of the drug, engendering a disconnection between thalamus, neocortex, and limbic areas. Given that ketamine-induced symptoms resemble the positive and negative symptoms of schizophrenia, they represent a consistent and novel pharmacological model to understand the molecular basis of hallucinations.

Notes

Acknowledgments

This chapter was supported by a grant from the AIFA (Proposal AIFA-2016-02364852).

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Gian Mario Mandolini
    • 1
  • Matteo Lazzaretti
    • 1
  • Alfredo Carlo Altamura
    • 1
  • Paolo Brambilla
    • 1
    • 2
    Email author
  1. 1.Department of Neurosciences and Mental Health, Fondazione IRCCS Ca’ Granda Ospedale Maggiore PoliclinicoUniversity of MilanMilanItaly
  2. 2.Department of Psychiatry and Behavioural NeurosciencesUniversity of Texas at HoustonHoustonUSA

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