期刊
NEUROPHARMACOLOGY
卷 39, 期 11, 页码 1974-1983出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0028-3908(00)00019-8
关键词
slices; microdialysis; serotonin release and uptake; awaking action
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 mu M) increased electrically-evoked, but not spontaneous, serotonin ([H-3]5-HT) efflux from cortical slices in a concentration-dependent manner while the indirect serotonin agonist dl-fenfluramine (1-15 mu M) enhanced both spontaneous and evoked [3H]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 mu M) and dl-fenfluramine (1-5 mu M), modafinil failed to influence the [H-3]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 mu M), 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-NT1A 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. (C) 2000 Elsevier Science Ltd. All rights reserved.
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