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Modafinil enhances the increase of extracellular serotonin levels induced by the antidepressant drugs fluoxetine and imipramine: A dual probe microdialysis study in awake rat
Author(s) -
Ferraro Luca,
Fuxe Kjell,
Agnati Luigi,
Tanganelli Sergio,
Tomasini Maria Cristina,
Antonelli Tiziana
Publication year - 2005
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20111
Subject(s) - dorsal raphe nucleus , imipramine , fluoxetine , modafinil , prefrontal cortex , microdialysis , pharmacology , chemistry , raphe nuclei , antidepressant , serotonin , endocrinology , medicine , psychology , dopamine , neuroscience , serotonergic , hippocampus , receptor , alternative medicine , cognition , pathology
In view of a postulated role of the vigilance‐promoting drug modafinil in depression, the interaction of modafinil and two classical antidepressant drugs, fluoxetine and imipramine, were studied in 5‐HT levels in the dorsal raphe‐cortical system using dual‐probe microdialysis. Fluoxetine (1–10 mg/kg) dose‐dependently increased dorsal raphe‐cortical 5‐HT levels. Modafinil at a very low dose (3 mg/kg), by itself ineffective, enhanced the fluoxetine (5 mg/kg)‐induced increases of 5‐HT levels in both brain areas. A synergistic interaction was observed in the prefrontal cortex with fluoxetine (1 mg/kg) in terms of 5‐HT release, but not in the dorsal raphe. Imipramine (1.3 mg/kg) increased 5‐HT levels in the dorsal raphe, but not in the prefrontal cortex, while the higher doses (10.9–21.8 mg/kg) caused substantial increases in both brain areas. Modafinil (3 mg/kg), injected before imipramine (1.3 mg/kg), which by itself was ineffective on cortical 5‐HT levels, increased cortical 5‐HT levels. On other hand, modafinil failed to affect the high‐dose imipramine (10.9 mg/kg)‐induced increase of 5‐HT levels in the prefrontal cortex and the imipramine (1.3; 10.9 mg/kg)‐induced increase of 5‐HT levels in the dorsal raphe nucleus. These results demonstrate that modafinil in low doses enhances the acute effects of fluoxetine and imipramine on 5‐HT levels in the dorsal raphe nucleus (fluoxetine only) and especially in the prefrontal cortex of the awake rat. These findings suggest a therapeutic potential of low doses of modafinil in the treatment of depression when combined with low doses of classical antidepressants, especially by increasing 5‐HT transmission in cortical regions. Synapse 55:230–241, 2005. © 2005 Wiley‐Liss, Inc.