NDLI: Potential brain neuronal targets for amphetamine-, methylphenidate-, and modafinil-induced wakefulness, evidenced by c-fos immunocytochemistry in the cat.

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Potential brain neuronal targets for amphetamine-, methylphenidate-, and modafinil-induced wakefulness, evidenced by c-fos immunocytochemistry in the cat.

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Potential brain neuronal targets for amphetamine-, methylphenidate-, and modafinil-induced wakefulness, evidenced by c-fos immunocytochemistry in the cat.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Hou, Y. Jouvet, M. Lin, J. S.
Description	Author Affiliation: Lin JS ( Départament de Médecine Expérimentale, Institut National de la Santé et de la Recherche Médicale Unité 52, Centre National de la Recherche Scientifique ERS 5645, Faculté de Médecine, Université Claude Bernard, Lyon, France. lin@cismsun.univ-lyonl);
Abstract	Much experimental and clinical data suggest that the pharmacological profile of modafinil, a newly discovered waking substance, differs from those of amphetamine and methylphenidate, two classical psychostimulants. The brain targets on which modafinil acts to induce wakefulness, however, remain unknown. A double-blind study using the protooncogene c-fos as experimental marker in the cat was, therefore, carried out to identify the potential target neurons of modafinil and compare them with those for amphetamine and methylphenidate. Cats were sacrificed after a single oral administration of amphetamine, methylphenidate, or modafinil at equivalent doses for wake induction (1, 2.5, or 5 mg/kg, respectively) and brain sections examined for Fos by immunocytochemistry. Administration of either amphetamine or methylphenidate evoked Fos-like immunoreactivity in a large number of neurons in the striatum and whole cortex, especially in the caudate nucleus and mediofrontal cortex, which are known to be dopaminergic targets. In contrast, administration of modafinil resulted in the labeling of few cells in these structures, but did induce marked Fos labeling in neurons of the anterior hypothalamic nucleus and adjacent areas. These results provide evidence for the potential brain targets of modafinil, which differ from those of amphetamine or methylphenidate, and suggest that modafinil induces wakefulness by mechanisms distinct from those of the two stimulants.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	24
Volume Number	93
Language	English
Publisher	National Academy of Sciences
Publisher Date	1996-01-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Amphetamine Pharmacology Benzhydryl Compounds Brain Physiology Central Nervous System Stimulants Genes, Fos Drug Effects Methylphenidate Neurons Proto-Oncogene Proteins C-fos Biosynthesis Wakefulness Animals Double-Blind Method Immunohistochemistry Metabolism Organ Specificity Research Support, Non-U.S. Gov't Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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