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Modafinil increases histamine release in the anterior hypothalamus of rats
Tomoko Ishizuka1, Yasuhiko Sakamoto, Toshimi Sakurai
1Department of Medical Physics, School of Allied Health Sciences, Faculty of Medicine, Osaka University, 1-7 Yamadaoka, Suita, Osaka 565-0871, Japan.
Abstract:
Modafinil, (RS)-2-(Diphenylmethylsulfinyl)acetamide, is a well known wake promoting drug used for the treatment of narcolepsy. We investigated the effect of modafinil on the hypothalamic histamine release in the anesthetized rat using in vivo microdialysis. Modafinil (150 mg/kg, i.p.) increased histamine release by 150% of the basal release. The intracerebroventricular (i.c.v.) injection of modafinil (1 nmol) also increased histamine release, however, when modafinil (1 nmol) was injected directly into the tuberomammillary nucleus, a limited region where cell bodies of the histaminergic neurons are located, histamine release was not altered. These observations suggest that modafinil may promote waking via the activation of the histaminergic system, although it does not appear to be a direct pharmacological target of modafinil.
Insights
Modafinil, a wake-promoting drug, significantly increases histamine release in the hypothalamus. This suggests modafinil may promote wakefulness by activating the histaminergic system.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Modafinil is a recognized wake-promoting agent used clinically for narcolepsy.
- The histaminergic system plays a crucial role in regulating arousal and wakefulness.
Purpose of the Study:
- To investigate the effect of modafinil on hypothalamic histamine release in vivo.
- To explore the potential role of the histaminergic system in modafinil's wake-promoting effects.
Main Methods:
- In vivo microdialysis in anesthetized rats.
- Administration of modafinil via intraperitoneal injection and intracerebroventricular (i.c.v.) injection.
- Direct injection of modafinil into the tuberomammillary nucleus (TMN).
Main Results:
- Modafinil administration (150 mg/kg, i.p.) increased basal histamine release by 150%.
- Intracerebroventricular (i.c.v.) injection of modafinil (1 nmol) also elevated histamine release.
- Direct injection of modafinil into the TMN did not alter histamine release.
Conclusions:
- Modafinil appears to promote wakefulness through the activation of the histaminergic system.
- The findings suggest that modafinil indirectly influences histaminergic neurons, rather than directly targeting them.