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

• Published in: Behavioural brain research Vol. 176; no. 2; pp. 353 - 357
• Main Authors: Murillo-Rodríguez, Eric, Haro, Reyes, Palomero-Rivero, Marcela, Millán-Aldaco, Diana, Drucker-Colín, René
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 25.01.2007; Elsevier Science
• Subjects: Analysis of Variance; Animals; Behavior, Animal - drug effects; Behavioral psychophysiology; Benzhydryl Compounds - pharmacology; Biological and medical sciences; Cannabinoid Receptor Modulators - pharmacology; Dopamine; Dopamine - metabolism; Drug Interactions; Endocannabinoid; Extracellular Fluid - drug effects; Fundamental and applied biological sciences. Psychology; Levodopa - metabolism; Male; Medical sciences; Microdialysis; Modafinil; Neuropharmacology; Neuroprotective Agents - pharmacology; Nucleus Accumbens - drug effects; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Psychopharmacology; Rats; Sleep; Sleep - drug effects; Time Factors; Wakefulness - drug effects; Wakefulness - physiology; Waking; Sleep; Dopamine; Microdialysis; Modafinil; Endocannabinoid; Waking; Rat; CNS stimulant; Psychotropic; Rodentia; Central nervous system; Basal ganglion; Catecholamine; Cannabinoid; Extracellular; Encephalon; Nucleus accumbens; Vertebrata; Mammalia; Wakefulness; Animal; Neurotransmitter; Sleep wake cycle
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2006.10.016

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 μg/5 μl) 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 μg/5 μl) to rats enhanced wakefulness (W) whereas diminished sleep during 4 h. 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.