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Beyond Dopamine Receptor Antagonism: New Targets for Schizophrenia Treatment and Prevention
Article

Sex-Specific Cannabidiol- and Iloperidone-Induced Neuronal Activity Changes in an In Vitro MAM Model System of Schizophrenia

1
Department of Molecular and Cellular Biology, University of Guelph, Guelph, ON N1G 2W1, Canada
2
Collaborative Program in Neuroscience, University of Guelph, Guelph, ON N1G 2W1, Canada
3
Department of Biomedical Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Felice Iasevoli
Int. J. Mol. Sci. 2021, 22(11), 5511; https://doi.org/10.3390/ijms22115511
Received: 6 April 2021 / Revised: 17 May 2021 / Accepted: 19 May 2021 / Published: 24 May 2021
Cortical circuit dysfunction is thought to be an underlying mechanism of schizophrenia (SZ) pathophysiology with normalization of aberrant circuit activity proposed as a biomarker for antipsychotic efficacy. Cannabidiol (CBD) shows potential as an adjunctive antipsychotic therapy; however, potential sex effects in these drug interactions remain unknown. In the present study, we sought to elucidate sex effects of CBD coadministration with the atypical antipsychotic iloperidone (ILO) on the activity of primary cortical neuron cultures derived from the rat methylazoxymethanol acetate (MAM) model used for the study of SZ. Spontaneous network activity measurements were obtained using a multielectrode array at baseline and following administration of CBD or ILO alone, or combined. At baseline, MAM male neurons displayed increased bursting activity whereas MAM female neurons exhibited no difference in bursting activity compared to sex-matched controls. CBD administered alone showed a rapid but transient increase in neuronal activity in the MAM networks, an effect more pronounced in females. Furthermore, ILO had an additive effect on CBD-induced elevations in activity in the MAM male neurons. In the MAM female neurons, CBD or ILO administration resulted in time-dependent elevations in neuronal activity, but the short-term CBD-induced increases in activity were lost when CBD and ILO were combined. Our findings indicate that CBD induces rapid increases in cortical neuronal activity, with sex-specific drug interactions upon ILO coadministration. This suggests that sex should be a consideration when implementing adjunct therapy for treatment of SZ. View Full-Text
Keywords: schizophrenia; cannabidiol; iloperidone; haloperidol; electrophysiology; primary cortical neurons schizophrenia; cannabidiol; iloperidone; haloperidol; electrophysiology; primary cortical neurons
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MDPI and ACS Style

Thériault, R.-K.; St-Denis, M.; Hewitt, T.; Khokhar, J.Y.; Lalonde, J.; Perreault, M.L. Sex-Specific Cannabidiol- and Iloperidone-Induced Neuronal Activity Changes in an In Vitro MAM Model System of Schizophrenia. Int. J. Mol. Sci. 2021, 22, 5511. https://doi.org/10.3390/ijms22115511

AMA Style

Thériault R-K, St-Denis M, Hewitt T, Khokhar JY, Lalonde J, Perreault ML. Sex-Specific Cannabidiol- and Iloperidone-Induced Neuronal Activity Changes in an In Vitro MAM Model System of Schizophrenia. International Journal of Molecular Sciences. 2021; 22(11):5511. https://doi.org/10.3390/ijms22115511

Chicago/Turabian Style

Thériault, Rachel-Karson; St-Denis, Myles; Hewitt, Tristen; Khokhar, Jibran Y.; Lalonde, Jasmin; Perreault, Melissa L. 2021. "Sex-Specific Cannabidiol- and Iloperidone-Induced Neuronal Activity Changes in an In Vitro MAM Model System of Schizophrenia" Int. J. Mol. Sci. 22, no. 11: 5511. https://doi.org/10.3390/ijms22115511

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