Effect of the Wake-Promoting Agent Modafinil on Sleep-Promoting Neurons from the Ventrolateral Preoptic Nucleus: an In Vitro Pharmacologic Study - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue SLEEP Année : 2004

Effect of the Wake-Promoting Agent Modafinil on Sleep-Promoting Neurons from the Ventrolateral Preoptic Nucleus: an In Vitro Pharmacologic Study

Résumé

The pharmacologic profile of modafinil, an increasingly popular wake-promoting drug for narcolepsy treatment, differs from those of classic psychostimulants such as amphetamine. However, its brain targets are still a matter of debate. We hypothesized that modafinil could increase waking by inhibiting the sleep-promoting neurons from the ventrolateral preoptic nucleus (VLPO). Such action could be direct or indirect via the potentiation of inhibition mediated by waking neurotransmitters. We thus studied the effect of modafinil on the membrane potential and firing rate of VLPO neurons recorded in rat-brain slices. We further determined whether pretreatment with modafinil modifies the effect of noradrenaline, carbachol, serotonin, histamine, dopamine, or clonidine. Measurements and Results: Pretreatment with modafinil specifically increased the inhibition of VLPO neurons induced by noradrenaline but had no effect when applied alone or in combination with other substances. Pretreatment with nisoxetine, a selective noradrenaline reuptake blocker, similarly increased the noradrenaline-induced inhibition of VLPO cells. Further, the potentiation by modafinil was minimized when modafinil and nisoxetine were applied together. Conclusions: These results suggest that modafinil blocks the reuptake of noradrenaline by the noradrenergic terminals on sleep-promoting neurons from the VLPO. Such a mechanism could be at least partially responsible for the wake-promoting effect of modafinil.
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Dates et versions

hal-00012376 , version 1 (11-02-2022)

Identifiants

  • HAL Id : hal-00012376 , version 1
  • PUBMED : 14998233

Citer

Thierry Gallopin, Luppi Pierre-Hervé, Francis Rambert, Armand Frydman, Patrice Fort. Effect of the Wake-Promoting Agent Modafinil on Sleep-Promoting Neurons from the Ventrolateral Preoptic Nucleus: an In Vitro Pharmacologic Study. SLEEP, 2004, 27 (1), pp.19-25. ⟨hal-00012376⟩
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