Modafinil enhances the increase of extracellular serotonin levels induced by the antidepressant drugs fluoxetine and imipramine: A dual probe microdialysis study in awake rat
by
Ferraro L, Fuxe K, Agnati L, Tanganelli S,
Tomasini MC, Antonelli T.
Department of Clinical and Experimental Medicine,
Section of Pharmacology,
University of Ferrara, Italy.
Synapse. 2005 Jan 24;55(4):230-241

ABSTRACT

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.

Mood
Serotonin
Glutamate
Modafinil: structure
Fluoxetine (Prozac)
Modafinil and the aviator
Modafinil: pharmacokinetics
Modafinil and the marmoset
Modafinil versus amphetamine
Modafinil versus methylphenidate
Modafinil v amphetamine v placebo
Modafinil plus SSRIs for depression and fatigue

Refs
and further reading

HOME
HedWeb
Nootropics
cocaine.wiki
Future Opioids
BLTC Research
MDMA/Ecstasy
Superhapiness?
Utopian Surgery?
The Abolitionist Project
The Hedonistic Imperative
The Reproductive Revolution
Critique of Huxley's Brave New World

The Good Drug Guide
The Responsible Parent's Guide
To Healthy Mood Boosters For All The Family