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Effects of Hallucinogens on Neuronal Activity.

L Lladó-Pelfort1, P Celada1, M S Riga1

  • 1Department of Neurochemistry and Neuropharmacology, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Institut d'Investigacions Biomèdiques de Barcelona (IIBB-CSIC-IDIBAPS), Barcelona, Spain.

Current Topics in Behavioral Neurosciences
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Summary

Hallucinogens like PCP and DOI alter brain activity, impacting neuronal firing and brain wave oscillations. Antipsychotic drugs can reverse these effects, suggesting a link to therapeutic mechanisms.

Keywords:
5-HT2A receptorsAntipsychotic drugsNMDA receptorsPrefrontal cortexThalamus

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Area of Science:

  • Neuroscience
  • Psychopharmacology
  • Computational Psychiatry

Background:

  • Hallucinogens produce sensory, perceptual, and cognitive effects relevant to mood and psychotic disorders.
  • Understanding the neurobiological basis of these disorders can be informed by studying psychotomimetic agents.

Purpose of the Study:

  • To review preclinical research on NMDA receptor antagonists and serotonergic hallucinogens.
  • To elucidate the mechanisms by which these agents alter cortical activity and their relationship to antipsychotic drug efficacy.

Main Methods:

  • Preclinical studies examining the effects of noncompetitive NMDA receptor (NMDA-R) antagonists (PCP, MK-801) and serotonergic hallucinogens (DOI, 5-MeO-DMT) on cortical activity in rodents.
  • Analysis of cellular and population activity in the prefrontal cortex (PFC) and other cortical areas.
  • Investigation of c-fos expression and thalamocortical network interactions.
  • Assessment of the effects of antipsychotic drugs on drug-induced alterations in brain activity.

Main Results:

  • Both NMDA-R antagonists and serotonergic hallucinogens altered pyramidal neuron discharge and attenuated low-frequency oscillations in the PFC.
  • PCP increased c-fos expression in excitatory neurons, particularly in the thalamus, by blocking NMDA-R on GABAergic neurons in the reticular nucleus.
  • Similar alterations in cortical activity were observed in other areas like the primary visual cortex (V1).
  • The disruption of PFC activity by PCP, DOI, and 5-MeO-DMT was reversed by antipsychotic medications.

Conclusions:

  • Noncompetitive NMDA-R antagonists and serotonergic hallucinogens induce comparable alterations in cortical activity, affecting neuronal firing and oscillations.
  • PCP's effects on thalamocortical networks involve the blockade of NMDA-R on specific GABAergic neurons.
  • The findings suggest a potential link between the perceptual disruptions caused by hallucinogens and the therapeutic mechanisms of antipsychotic drugs.