Effect fingerprints of antipsychotic drugs on neural networks in vitro

J Neural Transm (Vienna). 2019 Oct;126(10):1363-1371. doi: 10.1007/s00702-019-02050-8. Epub 2019 Jul 18.

Abstract

We compared the acute effect of typical (haloperidol) and atypical (aripiprazole, clozapine, olanzapine) antipsychotic drugs (APDs) on spontaneous electrophysiological activity of in vitro neuronal networks cultured on microelectrode arrays (MEAs). Network burst analysis revealed a "regularizing" effect of all APDs at therapeutic concentrations, i.e., an increase of network-wide temporal synchronization. At supratherapeutic concentrations, all APDs but olanzapine mediated a decrease of burst and spike rates, burst duration, number of spikes in bursts, and network synchrony. The rank order of potency of APDs was: haloperidol > aripiprazole > clozapine > olanzapine (no suppression). Disruption of network function was not due to enhanced cell death as assessed by trypan blue staining. APDs promoted distinct concentration-dependent alterations yielding acute effect fingerprints of the tested compounds. These effects were rather characteristic for individual compounds than distinctive for typical vs. atypical APDs. Thus, this dichotomy may be of value in distinguishing clinical features but has no apparent basis on the network or local circuitry level.

Keywords: Antipsychotic drugs; Microelectrode array; Network bursts; Neuronal network activity; Primary cortical culture.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects*
  • Action Potentials / physiology
  • Animals
  • Animals, Newborn
  • Antipsychotic Agents / pharmacology*
  • Aripiprazole / pharmacology
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / physiology
  • Clozapine / pharmacology
  • Dose-Response Relationship, Drug
  • Haloperidol / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Nerve Net / drug effects*
  • Nerve Net / physiology

Substances

  • Antipsychotic Agents
  • Aripiprazole
  • Clozapine
  • Haloperidol