Antidepressant-like effect of modafinil in mice: Evidence for the involvement of the dopaminergic neurotransmission.
BACKGROUND
Modafinil is a wake-promoting agent that provides wide ranges of neurological effects. There is evidence that it can produce antidepressant effects. This study investigated the antidepressant effect of modafinil in the tail suspension (TST) in mice.


METHODS
Different doses of modafinil was intraperitoneally (ip) administrated and then animals were subjected to TST and/or open field test (OFT). Moreover, the implication of the dopaminergic neurotransmission in modafinil's antidepressant effect was studied. For this purpose, animals were pretreated with haloperidol (non-selective dopamine receptor antagonist), or SCH23390 and sulpiride (the dopamine D1 and D2 receptor antagonist, respectively), then were assessed by TST. The possible effect of sub-effective dose of modafinil in combination with sub-therapeutic doses of standard antidepressants was also evaluated in separate groups.


RESULTS
Modafinil (75 mg/kg, ip) produced antidepressant effect in TST, as compared to a control group, without any alterations in ambulation in OFT. Pretreatment of mice with haloperidol (0.2mg/kg, ip) and sulpride (50mg/kg, ip) blocked the anti-immobility effect of modafinil (75 mg/kg, ip). We also found that the administration of SCH23390 (0.05 mg/kg, sc) couldn't antagonize the antidepressant effects of modafinil. In addition, a sub-effective dose of modafinil (50mg/kg, ip) potentiated the sub-effective doses of standard antidepressants including of bupropion (1mg/kg, ip), fluoxetine (1mg/kg, ip) and imipramine (0.1mg/kg, ip) and reduced immobility time in TST.


CONCLUSIONS
Results show that modafinil induced an antidepressant property in TST and this effect apparently was mediated through interaction with the dopaminergic (D2 receptors) system.
Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran.
Javad
J
Mahmoudi
Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran.
Mehdi
M
Farhoudi
Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran.
Mahnaz
M
Talebi
Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran.
Babak
B
Sabermarouf
Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran; Students Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: saeed.sadigetegad@gmail.com.
Saeed
S
Sadigh-Eteghad
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001559:Benzhydryl Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy* / Q000523:psychology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007103:Immobilization / Q000379:methods / Q000523:psychology; D008297:Male; D051379:Mice; D000077408:Modafinil; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D016896:Treatment Outcome
D000928:Antidepressive Agents; D001559:Benzhydryl Compounds; D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D000077408:Modafinil
D(2) dopamine receptor; Depression; Mice; Modafinil; Tail suspension test