Modafinil Induces Rapid-Onset Behavioral Sensitization and Cross-Sensitization with Cocaine in Mice: Implications for the Addictive Potential of Modafinil

Modafinil Induces Rapid-Onset Behavioral Sensitization and Cross-Sensitization with Cocaine in Mice: Implications for the Addictive Potential of Modafinil

Author Wuo-Silva, Raphael Autor UNIFESP Google Scholar
Fukushiro, Daniela Fukue Autor UNIFESP Google Scholar
Hollais, André Willian Autor UNIFESP Google Scholar
Santos-Baldaia, Renan Autor UNIFESP Google Scholar
Mari-Kawamoto, Elisa Autor UNIFESP Google Scholar
Berro, Laís Fernanda Autor UNIFESP Google Scholar
Yokoyama, Thais Suemi Autor UNIFESP Google Scholar
Lopes-Silva, Leonardo Brito Autor UNIFESP Google Scholar
Bizerra, Carolina Souza Autor UNIFESP Google Scholar
Procopio-Souza, Roberta Autor UNIFESP Google Scholar
Hashiguchi, Debora Autor UNIFESP Google Scholar
Figueiredo, Lilian A. Autor UNIFESP Google Scholar
Costa, Jose L. Google Scholar
Frussa-Filho, Roberto Autor UNIFESP Google Scholar
Longo, Beatriz Monteiro Autor UNIFESP Google Scholar
Abstract There is substantial controversy about the addictive potential of modafinil, a wake promoting drug used to treat narcolepsy, proposed as pharmacotherapy for cocaine abuse, and used indiscriminately by healthy individuals due to its positive effects on arousal and cognition. The rapid-onset type of behavioral sensitization (i.e., a type of sensitization that develops within a few hours from the drug priming administration) has been emerged as a valuable tool to study binge-like patterns of drug abuse and the neuroplastic changes that occur quickly after drug administration that ultimately lead to drug abuse. Our aim was to investigate the possible development of rapid-onset behavioral sensitization to modafinil and bidirectional rapid-onset cross sensitization with cocaine in male Swiss mice. A priming injection of a high dose of modafinil (64 mg/kg) induced rapid-onset behavioral sensitization to challenge injections of modafinil at the doses of 16, 32, and 64 mg/kg, administered 4 h later. Furthermore, rapid-onset cross-sensitization was developed between modafinil and cocaine (64 mg/kg modafinil and 20 mg/kg cocaine), in a bidirectional way. These results were not due to residual levels of modafinil as the behavioral effects of the priming injection of modafinil were no longer present and modafinil plasma concentration was reduced at 4 h post-administration. Taken together, the present findings provide preclinical evidence that modafinil can be reinforcing per se and can enhance the reinforcing effects of stimulants like cocaine within hours after administration.
Keywords cocaine
drug abuse
open field
rapid-onset behavioral sensitization
xmlui.dri2xhtml.METS-1.0.item-coverage Lausanne
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Fundo de Auxílio aos Docentes e Alunos (FADA)
Associação Fundo de Incentivo à Psicofarmacologia (AFIP)
Grant number FAPESP: 2014/24277-4
Date 2016
Published in Frontiers In Pharmacology. Lausanne, v. 7, p. -, 2016.
ISSN 1663-9812 (Sherpa/Romeo, impact factor)
Publisher Frontiers Media Sa
Extent -
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000387083100001

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