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

Autor: Melissa L. Perreault, Jibran Y. Khokhar, Myles St-Denis, Rachel-Karson Thériault, Tristen Hewitt, Jasmin Lalonde
Rok vydání: 2021
Předmět:
Male
0301 basic medicine
medicine.medical_treatment
Cell Culture Techniques
Pharmacology
haloperidol
Rats
Sprague-Dawley
cannabidiol
chemistry.chemical_compound
Iloperidone
0302 clinical medicine
Piperidines
Haloperidol
Premovement neuronal activity
Biology (General)
Spectroscopy
Cerebral Cortex
Neurons
Sex Characteristics
Methylazoxymethanol acetate
General Medicine
Computer Science Applications
Chemistry
iloperidone
surgical procedures
operative
Female
Antipsychotic Agents
medicine.drug
QH301-705.5
medicine.drug_class
Atypical antipsychotic
digestive system
Article
Catalysis
Inorganic Chemistry
03 medical and health sciences
medicine
Animals
Physical and Theoretical Chemistry
Antipsychotic
QD1-999
Molecular Biology
business.industry
Organic Chemistry
Isoxazoles
electrophysiology
digestive system diseases
Rats
schizophrenia
Disease Models
Animal
Electrophysiology
030104 developmental biology
Animals
Newborn
chemistry
primary cortical neurons
business
Cannabidiol
030217 neurology & neurosurgery
Zdroj: International Journal of Molecular Sciences, Vol 22, Iss 5511, p 5511 (2021)
International Journal of Molecular Sciences
Volume 22
Issue 11
ISSN: 1422-0067
DOI: 10.3390/ijms22115511
Popis: 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.
Databáze: OpenAIRE
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