, Volume 345, Issue 4, pp 461-465

Inhibitory effects of the psychoactive drug modafinil on γ-aminobutyric acid outflow from the cerebral cortex of the awake freely moving guinea-pig

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The effects of modafmil on acetylcholine and GABA outflow from the cerebral cortex of awake freely moving guinea pigs provided with an epidural cup were studied. In the dose range of 3–30 mg/kg s. c. modafmil produced a dose dependent significant inhibition of GABA outflow without influencing cortical acetylcholine release. Methysergide (2 mg/kg, i.p.) and ketanserin (0.5 mg/kg, i. p.) but not prazosin (0.14 mg/kg, i. p.) counteracted the inhibitory action of modafinil on cortical GABA outflow. Modafinil both acutely and chronically in the same dose range increased striatal 5-HIAA levels and 5-HT utilization in the rat (acute) and mouse (chronic). The action on cortical GABA release may be dependent on activity at 5-HT2 receptors, since the action of modafmil in this respect is blocked by the non-selective 5-HT antagonist methysergide and the 5-HT2 antagonist ketanserin. The involvement of 5-HT mechanisms in the inhibitory action of modafmil on cortical GABA release is also suggested by the findings that 5-HT metabolism may become increased by modafmil at least in the striatum. The reduction of cortical GABA outflow via 5-HTZ receptors by modafmil is probably related to some of its actions on the central nervous system including behavioural effects.

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