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Published on: June 12, 2018
Chronic haloperidol increases voltage-gated Na+ currents in mouse cortical neurons
Weiqiang Chen1, Fangfang Zhu2, Jingfang Guo3
1Department of Neurosurgery, First Affiliated Hospital, Shantou University Medical College, 57 Changping Road, Shantou, Guangdong 515041, China; Department of Microbiology and Immunology, Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, 22 Xinling Road, Shantou, Guangdong 515041, China.
Typical antipsychotics like haloperidol initially inhibit neuronal voltage-gated sodium channels (VGSCs). However, chronic exposure enhances VGSC activity, potentially explaining extrapyramidal syndrome (EPS).
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- Typical antipsychotics are known to cause extrapyramidal syndrome (EPS).
- Previous research indicated that these drugs inhibit neuronal voltage-gated sodium channels (VGSCs).
- The onset of EPS often requires prolonged drug exposure.
Purpose of the Study:
- To investigate the effects of haloperidol, a typical antipsychotic, on neuronal VGSCs over varying exposure durations.
- To understand the temporal relationship between antipsychotic exposure and VGSC activity.
- To explore the molecular mechanisms underlying these effects.
Main Methods:
- Utilized whole-cell patch-clamp technique to record VGSC currents.
- Employed primary cultures of mouse cortical neurons.
- Examined effects after acute (minutes) and chronic (hours) haloperidol exposure.
Main Results:
- Acute haloperidol exposure inhibited VGSC activity.
- Chronic haloperidol exposure enhanced VGSC currents in a time- and concentration-dependent manner.
- Chronic exposure led to increased VGSC subunit expression and altered channel properties.
Conclusions:
- Found contrasting effects of haloperidol on VGSCs: inhibition with acute exposure and enhancement with chronic exposure.
- Enhanced VGSC currents following chronic haloperidol exposure in cortical neurons were observed.
- These findings may contribute to the understanding of the mechanisms behind typical antipsychotic-induced EPS.
