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Dopamine-cell depolarization block as a model for the therapeutic actions of antipsychotic drugs
Open accessAbstract
Antipsychotic drugs used in the treatment of schizophrenia have in common the property of being dopamine-receptor antagonists. However, the rapid timecourse of receptor blockade produced upon drug administration does not correlate with the emergence of clinical actions, which typically require weeks of treatment to become manifest. Studies in rats have shown that repeated antipsychotic drug treatment results in a delayed inactivation of dopamine-neuron firing in the midbrain due to depolarization block. Furthermore, the therapeutic efficacy of antipsychotic drugs in humans correlates with their ability to induce depolarization block of mesolimbic dopamine neurons, whereas their potential to produce extrapyramidal side effects correlates with their propensity for inducing depolarization block in the nigrostriatal dopamine system. Therefore, dopamine-cell depolarization block is an effective model for evaluating antipsychotic drug efficacy, and provides a potential mechanism to account for their therapeutic impact on a dysregulated dopamine system.
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Citations
Cited by
The Dopamine Hypothesis of Schizophrenia: Version III--The Final Common Pathway
Howes, O. D., & Kapur, S. (2009) · Schizophrenia Bulletin · doi:10.1093/schbul/sbp006 · Cited by 2,693
The hippocampal-VTA loop: controlling the entry of information into long-term memory
Lisman, J. E., & Grace, A. A. (2005) · Neuron · doi:10.1016/j.neuron.2005.05.002 · Cited by 1,983
Self-citationTrajectories of brain development: point of vulnerability or window of opportunity?
Andersen, S. L. (2003) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(03)00005-8 · Cited by 1,503
Regulation of firing of dopaminergic neurons and control of goal-directed behaviors
Grace, A. A., Floresco, S. B., Goto, Y., & Lodge, D. J. (2007) · Trends in Neurosciences · doi:10.1016/j.tins.2007.03.003 · Cited by 1,034
Self-citationMiyamoto, S., Duncan, G. E., Marx, C. E., & Lieberman, J. A. (2005) · Molecular Psychiatry · doi:10.1038/sj.mp.4001556 · Cited by 988
Metadata
- Authors
- Grace, A. A., Bunney, B. S., Moore, H., & Todd, C. L.
- Venue
- Trends in Neurosciences
- Publisher
- Elsevier BV
- Published
- 1997-01
- Volume
- 20
- Issue
- 1
- Pages
- 31-37
- ISSN
- 0166-2236 (ISSN-L)
- OpenAlex
- W2015701330
- Cited by
- 284
- References
- 0
- FWCI
- 3.14
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Grace, A. A., Bunney, B. S., Moore, H., & Todd, C. L. (1997). Dopamine-cell depolarization block as a model for the therapeutic actions of antipsychotic drugs. Trends in Neurosciences. https://doi.org/10.1016/s0166-2236(96)10064-3
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
