Effects of the vigilance promoting drug modafinil on the synthesis of GABA and glutamate in slices of rat hypothalamus

The effects of the vigilance promoting drug modafil were studied ex vivo (100 mg/kg; i.p.) and in vitro (10-1000 mu M modafinil) on the synthesis of [H-3]gamma-aminobutyric acid ([H-3]GABA) and [H-3]glutamate from [H-3]glutamine within the rat hypothalamus. No effects of modafinil were observed on the overall synthesis of these neurotransmitters nor, in vitro (1-33 mu M modafinil) on other parameters related to the compartmentalization of their synthesis (glutamate decarboxylase and phosphate-activated glutaminase activities, and [H-3]glutamine uptake). It is suggested on these grounds, that the modafinil-induced reductions and increases in regional GABA and glutamate extracellular levels respectively using in vivo microdialysis may be a consequence of an indirect effect of modafinil on these neurons. (C) 1999 Elsevier Science ireland Ltd. All rights reserved.