Modafinil enhances extracellular levels of dopamine in the nucleus accumbens and increases wakefulness in rats

Behav Brain Res. 2007 Jan 25;176(2):353-7. doi: 10.1016/j.bbr.2006.10.016. Epub 2006 Nov 13.

Abstract

Modafinil (MOD) is a wakefulness-promoting drug that improves the alertness levels in narcolepsy; however, the molecular mechanism of action remains to be elucidated. We found that after a single icv injection of MOD (10 microg/5 microl) the extracellular levels of dopamine (DA) and l-DOPA collected from the nucleus accumbens were increased and decreased, respectively. Separately, the icv administration of MOD (10 microg/5 microl) to rats enhanced wakefulness (W) whereas diminished sleep during 4h. Lastly, the alertness induced by MOD was partially antagonized by the sleep-inducing endocannabinoid anandamide (ANA). We conclude that MOD enhances the extracellular levels of DA, promotes W and its effects on sleep are partially blocked by ANA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Behavior, Animal / drug effects
  • Benzhydryl Compounds / pharmacology*
  • Cannabinoid Receptor Modulators / pharmacology
  • Dopamine / metabolism*
  • Drug Interactions
  • Extracellular Fluid / drug effects*
  • Levodopa / metabolism
  • Male
  • Modafinil
  • Neuroprotective Agents / pharmacology*
  • Nucleus Accumbens / drug effects*
  • Rats
  • Sleep / drug effects
  • Time Factors
  • Wakefulness / drug effects*
  • Wakefulness / physiology

Substances

  • Benzhydryl Compounds
  • Cannabinoid Receptor Modulators
  • Neuroprotective Agents
  • Levodopa
  • Modafinil
  • Dopamine