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Modafinil: an antinarcoleptic drug with a different neurochemical profile to d-amphetamine and dopamine uptake blockers
No full textTo examine the biochemical differences between modafinil
and dopaminergic-releasing drugs, the purpose of the present
microdialysis study was to compare the effects of modafinil,
d-amphetamine, and dopamine uptake blockers on DA and
GABA release in the rat nucleus accumbens
Modafinil prevents glutamate cytotoxicity in cultured cortical neurons
No full textThe ability of modafinil (Modiodal) to protect cortical neurons from glutamate-induced degeneration was evaluated by measuring electrically evoked [3H]GABA release and [3H]GABA uptake in primary cerebral cortical cultures. In normal cells, electrical stimulation (10 Hz, 2 min) increased [3H]GABA release (FR-NER St1 = 0.77+/-0.14; St2/St1 ratio = 0.94+/-0.02). The exposure of sister cells to glutamate, reduced electrically evoked [3H]GABA release (FR-NER St1 = 0.40+/-0.05; St2/St1 ratio = 0.60+/-0.08). Modafinil (0.3-1 microM) prevented the glutamate-induced reduction of the St2/St1 ratio (0.85+/-0.11; 0.88+/-0.05, respectively). A similar protective effect was observed for [3H]GABA uptake. These findings suggest that modafinil may be neuroprotective in that it attenuates glutamate-induced excitotoxicity in cortical neurons
Preclinical studies with modafinil. Evidence for vigilance enhancement and neuroprotection
No full textModafinil, which is presently used in the treatment of narcolepsy, induces EEG arousal in mammals, including rhesus monkeys and produces behavioral arousal in mice and rats without the induction of stereotyped behaviors. Pharmacological analysis suggests an indirect involvement of central alpha(1)-adrenergic mechanisms but not of dopamine systems in the behavioral activating action of modafinil. Studies on the neurochemical mechanisms of the vigilance promoting actions of modafinil show no or only weak effects on brain monoamides. It is of interest that modafinil can increase glutamine synthase mRNA and protein in various brain regions, suggesting an activation of astrocyte metabolism through wakefulness produced by modafinil and leading to energy production. The major neurochemical action of modafinil, however, appears to be a reduction of GABA release in several brain regions, such as the cerebral cortex and the nucleus accumbens, which is dependent upon 5-HT receptor activation. Increases of dopamine release in the rat nucleus accumbens appears to involve the inactivation of a local GABAergic mechanism. It is postulated that a reduction of GABA release plays a relevant role in the wakefulness produced by modafinil, especially in view of the strong inhibitory regulation by GABA of the excitatory glutamate pathways. Modafinil has also been shown to produce neuroprotective effects in three different types of lesion models, namely a neurotoxic model with MPTP (parkinsonian model), a mechanical trauma model involving partial hemitransection at the di-and telencephalic level, acid a local ischemia model involving ET-1 induced injury. Modafinil will therefore be of clinical relevance not only in sleep disorders but could also find potential applications in the treatment of neurodegenerative diseases such as Parkinson's disease and stroke
The effects of modafinil on striatal, pallidal and nigral GABA and glutamate release in the conscious rat: evidence for a preferential inhibition of striato-pallidal GABA transmission.
No full textThe effects of the anti-narcoleptic drug modafinil (30-300 mg/kg i.p.) on GABA and glutamate release were evaluated in the basal ganglia of the conscious rat, by using the microdialysis technique. Modafinil (100 mg/kg) inhibited striatal (85+/-4% of basal values) and pallidal (85+/-2%) GABA release without influencing local glutamate release. At the highest dose (300 mg/kg), modafinil induced a further reduction of pallidal (75+/-2%) but not striatal (82+/-7%) GABA release and increased striatal (134+/-11%) but not pallidal glutamate release. On the contrary, in the substantia nigra modafinil reduced GABA release only at the 300 mg/kg dose (59+/-5%) without affecting glutamate release. The preferential reduction in striato-pallidal GABA release at the 100 mg/kg dose of modafinil suggests that modafinil may be useful in the treatment of Parkinsonian diseases
Modafinil and cortical γ-aminobutyric acid outflow. Modulation by 5-hydroxytryptamine neurotoxins
No full textThe acute or chronic administration of modafinil, (diphenyl-methyl-sulfinyl-2-acetamide, 30 mg/kg s.c.) decreased gamma-amino-butyric acid (GABA) outflow from the cerebral cortex of freely moving guinea pigs and rats. In 5,7-dihydroxytryptamine intracerebroventricularly pretreated guinea pigs, the effect of modafinil on GABA outflow was reversed and the noradrenaline cortical levels increased. Prazosin (35.8 ng/kg i.p.) blocked the drug-induced increase in GABA efflux. In vitro experiments, performed in rat cortical slices, showed that modafinil failed to affect [3H]GABA release and uptake as well as glutamic acid decarboxylase activity. In conclusion, our results suggest that the balance between central noradrenaline and 5-hydroxytryptamine transmission is important for the regulation by modafinil of the GABAergic release in the cerebral cortex
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
The vigilance promoting drug modafinil increases extracellular glutamate levels in the medial preoptic area and the posterior hypothalamus of the conscious rat: prevention by local GABAA receptor blockade
No full textThe effects of modafinil on glutamatergic and GABAergic transmission in the rat medial preoptic area (MPA) and posterior hypothalamus (PH), are analysed. Modafinil (30-300 mg/kg) increased glutamate and decreased GABA levels in the MPA and PH. Local perfusion with the GABAA agonist muscimol (10 microM), reduced, while the GABAA antagonist bicuculline (1 microM and 10 microM) increased glutamate levels. The modafinil (100 mg/kg)-induced increase of glutamate levels was antagonized by local perfusion with bicuculline (1 microM). When glutamate levels were increased by the local perfusion with the glutamate uptake inhibitor L-trans-PDC (0.5 mM), modafinil produced an additional enhancement of glutamate levels. Modafinil (1-33 microM) failed to affect [3H]glutamate uptake in hypothalamic synaptosomes and slices. These findings show that modafinil increases glutamate and decreases GABA levels in MPA and PH. The evidence that bicuculline counteracts the modafinil-induced increase of glutamate levels strengthens the evidence for an inhibitory GABA/glutamate interaction in the above regions controlling the sleep-wakefulness cycle
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