Implications of Cellular Models of Dopamine Neurons for Schizophrenia
Open accessAbstract
Midbrain dopamine neurons are pacemakers in vitro, but in vivo they fire less regularly and occasionally in bursts that can lead to a temporary cessation in firing produced by depolarization block. The therapeutic efficacy of antipsychotic drugs used to treat the positive symptoms of schizophrenia has been attributed to their ability to induce depolarization block within a subpopulation of dopamine neurons. We summarize the results of experiments characterizing the physiological mechanisms underlying the ability of these neurons to enter depolarization block in vitro, and our computational simulations of those experiments. We suggest that the inactivation of voltage-dependent Na(+) channels, and, in particular, the slower component of this inactivation, is critical in controlling entry into depolarization block. In addition, an ether-a-go-related gene (ERG) K(+) current also appears to be involved by delaying entry into and speeding recovery from depolarization block. Since many antipsychotic drugs share the ability to block this current, ERG channels may contribute to the therapeutic effects of these drugs.
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Treatment with the antipsychotics raclopride, sulpiride, and olanzapine in vitro rescued the resting membrane potential deficit.
“Interestingly, treatment with the antipsychotics raclopride, sulpiride, and olanzapine in vitro, which modulate neuronal excitability51,56,57, rescued the RMP deficit.”
From Neuronal defects in a human cellular model of 22q11.2 deletion syndrome (2020) · cites this paper as [56]
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- Authors
- Yu, N., Tucker, K. R., Levitan, E. S., Shepard, P. D., & Canavier, C. C.
- Affiliations
- Louisiana State University Health Sciences Center New Orleans (US)
- University of Pittsburgh (US)
- University of Maryland, Baltimore (US)
- Venue
- Progress in Molecular Biology and Translational Science
- Publisher
- Elsevier
- Published
- 2014
- Volume
- 123
- Pages
- 53-82
- ISSN
- 1877-1173 (ISSN-L)
- PMC
- PMC4351765
- OpenAlex
- W2405918807
- Cited by
- 17
- References
- 46
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 2 · 2019: 1 · 2017: 2 · 2015: 1 · 2014: 5
- FWCI
- 3.37
- Type
- book chapter
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Progress in molecular biology and translational science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (P30GM103340)
- National Institute of Neurological Disorders and Stroke (R01NS061097)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- midbrain dopaminergic neurons, depolarization block, schizophrenia, antipsychotic drugs, neuronal firing patterns, computational modeling, positive symptoms
- MeSH terms
- Action Potentials, Animals, Humans, Models, Neurological, Schizophrenia, Antipsychotic Agents, Ion Channel Gating, Dopaminergic Neurons
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