The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.
Hypothalamic Arousal Regions Are Activated during Modafinil-Induced Wakefulness
Open accessAbstract
Modafinil is an increasingly popular wake-promoting drug used for the treatment of narcolepsy, but its precise mechanism of action is unknown. To determine potential pathways via which modafinil acts, we administered a range of doses of modafinil to rats, recorded sleep/wake activity, and studied the pattern of neuronal activation using Fos immunohistochemistry. To contrast modafinil-induced wakefulness with spontaneous wakefulness, we administered modafinil at midnight, during the normal waking period of rats. To determine the influence of circadian phase or ambient light, we also injected modafinil at noon on a normal light/dark cycle or in constant darkness. We found that 75 mg/kg modafinil increased Fos immunoreactivity in the tuberomammillary nucleus (TMN) and in orexin (hypocretin) neurons of the perifornical area, two cell groups implicated in the regulation of wakefulness. This low dose of modafinil also increased the number of Fos-immunoreactive (Fos-IR) neurons in the lateral subdivision of the central nucleus of the amygdala. Higher doses increased the number of Fos-IR neurons in the striatum and cingulate cortex. In contrast to previous studies, modafinil did not produce statistically significant increases in Fos expression in either the suprachiasmatic nucleus or the anterior hypothalamic area. These observations suggest that modafinil may promote waking via activation of TMN and orexin neurons, two regions implicated in the promotion of normal wakefulness. Selective pharmacological activation of these hypothalamic regions may represent a novel approach to inducing wakefulness.
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Cites
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Cited by
Differential expression of orexin receptors 1 and 2 in the rat brain
Marcus, J. N., Aschkenasi, C. J., Lee, C. E., Chemelli, R. M., Saper, C. B., Yanagisawa, M., & Elmquist, J. K. (2001) · Journal of Comparative Neurology · doi:10.1002/cne.1190 · Cited by 1,659
Self-citationSleep Deprivation and Vigilant Attention
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Modafinil: a review of neurochemical actions and effects on cognition
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Self-citationFos Expression in Orexin Neurons Varies with Behavioral State
Estabrooke, I. V., McCarthy, M. T., Ko, E., Chou, T. C., Chemelli, R. M., Yanagisawa, M., Saper, C. B., & Scammell, T. E. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-05-01656.2001 · Cited by 654
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Metadata
- Authors
- Scammell, T. E., Estabrooke, I. V., McCarthy, M. T., Chemelli, R. M., Yanagisawa, M., Miller, M. S., & Saper, C. B.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2000-11-15
- Volume
- 20
- Issue
- 22
- Pages
- 8620-8628
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- OpenAlex
- W1945000294
- Cited by
- 485
- References
- 40
- FWCI
- 13.56
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Scammell, T. E., Estabrooke, I. V., McCarthy, M. T., Chemelli, R. M., Yanagisawa, M., Miller, M. S., & Saper, C. B. (2000). Hypothalamic Arousal Regions Are Activated during Modafinil-Induced Wakefulness. The Journal of Neuroscience. https://doi.org/10.1523/jneurosci.20-22-08620.2000
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