Summary
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.
Access this article
We’re sorry, something doesn't seem to be working properly.
Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.
Similar content being viewed by others
References
Antonelli T, Beani L, Bianchi C, Rando S, Simonato M, Tanganelli S (1986) Cortical acetylcholine release is increased and aminobutyric acid outflow is reduced during morphine withdrawal. Br J Pharm 89:853–860
Aston-Jones G (1985) Behavioural functions of locus coeruleus derived from cellular attributes. Physiol Psychol 13:118–126
Beani L, Bianchi C, Giacomelli A, Tamberi F (1978) Noradrenaline inhibition of acetylcholine release from guinea-pig brain. Eur J Pharmacol 48:89–93
Beani L, Bianchi C, Tanganelli S, Antonelli T, Simonato M, Rando S (1988) Inversion of the α-2 and α-1 noradrenergic control on the cortical release of acetylcholine and γ-aminobutyric acid in morphine tolerant guinea-pig. Pharmacol Exp Ther 247:294–301
Beani L, Tanganelli S, Antonelli T, Simonato M, Spalluto C, Tomasini C, Bianchi C (1989) Changes in cortical acetylcholine and γ-aminobutyric acid outflow during morphine withdrawal involve α-1 and α-2 receptors. J Pharmacol Exp Ther 250:682–687
Bianchi C, Siniscalchi A, Beani L (1986) The influence of 5-hydroxytryptamine of the release of acetylcholine from guinea-pig brain ex vivo and in vitro. Neuropharmacology 25:1043–1049
Bianchi C, Siniscalchi A, Beam L (1989) Effect of 5-hydroxytryptamine on 3H-acetylcholine release from guinea-pig striatal slices. Br J Pharmacol 97:213–221
Casamenti F, Bianchi C, Beani L, Pepeu G (1980) Effects of haloperidol and pimozide on acetylcholine output from the cerebral cortex in rats and guinea-pigs. Eur J Pharmacol 65:279–284
Duteil J, Rambert FA, Pessonnier J, Hermant J-F, Gomberg R, Assous E (1990) Central α-1 adrenergic stimulation in relation to the behaviour stimulating effect of modafinil; studies with experimental animals. Eur J Pharmacol 180:49–58
Hollander M, Wolfe DA (1973) Non-parametric statistical methods. Wiley, New York
Keller R, Oke A, Mefford I, Adams RN (1976) The use of liquid chromatographic analysis of catecholamines-routine assay of regional brain mapping. Life Sci 19:995–1004
Leysen JE, Niemegeers CJE, Van Nueten JM, Laduron PM (1982) 3H-Ketanserin (R-41 468), a selective 3H-ligand for serotonin2 receptor binding sites. Mol Pharmacol 21:301–314
Limberger N, Spath L, Starke K (1986) A search for receptors modulating the release of γ-3H-aminobutyric acid in rabbit caudate nucleus slices. J Neurochem 46:1109–1117
Luthman J (1989) Neonatal dopamine lesions: morphological, biochemical and behavioural characterization. Thesis ISBN 917900–864-X, Karolinska Institute, Stockholm
Mayer ML, Straughan DW (1981) Effects of 5-hydroxytryptamine on central neurons antagonized by bicuculline and picrotoxin. Neuropharmacology 20:347–350
Marien MR, Richard JW (1990) Drug effects on the release of endogenous acetylcholine in vivo: measurement by intracerebral dialysis and gas chromatography-mass spectrometry. J Neurochem 54:2016–2023
Peroutka SJ (1988) 5-Hydroxytryptamine receptor subtypes. Ann Rev Neurosci 11:45
Rambert FA, Pessonnier L, Duteil J (1990) Modafinil, amphetamine and methylphenidate induced hyperactivities in mice involve different mechanisms. Eur J Pharmacol 183:455–456
Siniscalchi A, Beani L, Bianchi C (1990) Different effects of 8–0H-DPAT, a 5-HT1A receptor agonist, on cortical acetylcholine release, electrocorticogram and body temperature in guinea-pigs and rats. Eur J Pharmacol 175:219–223
Smythe JW, Pappas BA (1989) Noradrenergic and serotoninergic mediation of the locomotor and antinociceptive effects of clonidine in infant and adult rats. Pharmacol Biochem Behav 34:413–418
Soubrie P, Reisine TD, Glowinsky J (1984) Functional aspects of serotonin transmission in the basal ganglia: a review and an in vivo approach using the push-pull cannula technique. Neuroscience 13:605–625
Vizi ES (1980) Modulation of cortical release of acetylcholine by noradrenaline released from nerves arising from rat locus coeruleus. Neuroscience 5:2139–2144
Author information
Authors and Affiliations
Additional information
Send offprint requests to K. Fuxe at the above address
Rights and permissions
About this article
Cite this article
Tanganelli, S., Fuxe, K., Ferraro, L. et al. Inhibitory effects of the psychoactive drug modafinil on γ-aminobutyric acid outflow from the cerebral cortex of the awake freely moving guinea-pig. Naunyn-Schmiedeberg's Arch Pharmacol 345, 461–465 (1992). https://doi.org/10.1007/BF00176625
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00176625