Antidepressant-like effect of modafinil in mice: Evidence for the involvement of the dopaminergic neurotransmission

Abstract

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 D-1 and D-2 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 (0.2 mg/kg, ip) and sulpride (50 mg/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 (50 mg/kg, ip) potentiated the sub-effective doses of standard antidepressants including of bupropion (1 mg/kg, ip), fluoxetine (1 mg/kg, ip) and imipramine (0.1 mg/kg, ip) and reduced immobility time in TST. Conclusion: Results show that modafinil induced an antidepressant property in TST and this effect apparently was mediated through interaction with the dopaminergic (D-2 receptors) system. (C) 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Sp. z o.o. All rights reserved.