Amplification of cortical serotonin release: a further neurochemical action of the vigilance-promoting drug modafinil

Ferraro L, Fuxe K, Tanganelli S,
Fernandez M, Rambert FA, Antonelli T

Department of Experimental and Clinical Medicine,
Section of Pharmacology, University of Ferrara, Ferrara, Italy
Neuropharmacology 2000 Oct 1; 39(11):1974-1983

ABSTRACT

The present in vitro and in vivo studies examined the effects of modafinil on serotonergic transmission in the rat frontal cortex. In the in vitro study modafinil (0.3-30 muM) increased electrically-evoked, but not spontaneous, serotonin ([(3)H]5-HT) efflux from cortical slices in a concentration-dependent manner while the indirect serotonin agonist dl-fenfluramine (1-15 muM) enhanced both spontaneous and evoked [(3)H]5-HT efflux. The effects of modafinil were more pronounced when the 5-HT reuptake was blocked by paroxetine. Contrary to paroxetine (0.3-3 muM) and dl-fenfluramine (1-5 muM), modafinil failed to influence the [(3)H]5-HT uptake. In the in vivo study modafinil (3-100 mg/kg i.p.) increased 5-HT dialysate levels, the maximal effect being already reached at the 30 mg/kg dose. dl-fenfluramine (5 mg/kg) induced an increase in 5-HT levels which was significantly higher than that displayed by modafinil at 30 mg/kg. In the presence of paroxetine (3 muM), the effect of modafinil at 30 mg/kg was higher than that observed in the absence of 5-HT reuptake inhibition.  Finally, in the presence of the selective 5-HT(1A) receptor agonist 8-OH-DPAT, modafinil at 100 mg/kg failed to affect 5-HT dialysate levels.These results demonstrate that modafinil regulates cortical serotonergic transmission and suggest that the drug preferentially acts by amplifying the electro-neurosecretory coupling mechanisms and via mechanisms which do not involve the reuptake process.

Modafinil research

 1.   Modafinil  for sustaining the alertness of helicopter pilots
 2.   Modafinil  augmentation of antidepressant treatment
 3.   Modafinil  the unique properties of a new stimulant 
 4.   Modafinil  children with attention-deficit/hyperactivity disorder
 5.   Modafinil  tolerability in healthy male volunteers
 6.   Modafinil  successful treatment of hypersomnia & narcolepsy
 7.   Modafinil  narcolepsy: symptoms and management
 8.   Modafinil  amplification of cortical serotonin release
 9.   Modafinil  treatment of alcoholic organic brain syndrome
10.  Modafinil  effect on melatonin, cortisol, and growth hormone
11.  Modafinil  in obstructive sleep apnea-hypopnea syndrome

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