Modafinil enhances extracellular levels of dopamine in the nucleus accumbens and increases wakefulness in rats.
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.
Murillo-Rodríguez
Eric
E
Depto de Neurociencias, Instituto de Fisiología Celular, Ciudad Universitaria, Circuito Interior, Universidad Nacional Autónoma de México, C.P. 04510, México D.F., Mexico. emurillo@ifc.unam.mx
Haro
Reyes
R
Palomero-Rivero
Marcela
M
Millán-Aldaco
Diana
D
Drucker-Colín
René
R
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D063385:Cannabinoid Receptor Modulators / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004347:Drug Interactions; D045604:Extracellular Fluid / Q000187:drug effects*; D007980:Levodopa / Q000378:metabolism; D008297:Male; D000077408:Modafinil; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects*; D051381:Rats; D012890:Sleep / Q000187:drug effects; D013997:Time Factors; D014851:Wakefulness / Q000187:drug effects* / Q000502:physiology
D001559:Benzhydryl Compounds; D063385:Cannabinoid Receptor Modulators; D018696:Neuroprotective Agents; D007980:Levodopa; D000077408:Modafinil; D004298:Dopamine