Potencial de abuso do modafinil e sensibilização cruzada com cocaína: um estudo pré-clínico. / Addictive potencial of modafinil and cross-sensitization with cocaine: a preclinical study.

AUTOR(ES)
DATA DE PUBLICAÇÃO

2010

RESUMO

Repeated or even a single exposure to all addictive drugs causes persistent locomotor sensitization, which is the result of an abundance of neuroplastic changes occurring within the circuitry involved in motivational behavior and is thought to play a key role in certain aspects of drug addiction. There is substantial controversy about the addictive potential of modafinil, a wake-promoting drug used to treat narcolepsy that is increasingly being used as a cognitive enhancer and has been proposed as a pharmacotherapy for cocaine dependence. We investigated the ability of modafinil to induce locomotor sensitization after repeated or single administration in mice. Bi-directional crosssensitization with cocaine and modafinil-induced conditioned place preference were also evaluated. Both repeated and single exposure to modafinil produced a pronounced locomotor sensitization that cross-sensitized in a bi-directional way with cocaine. Remarkably, when cocaine and modafinil were repeatedly administered sequentially, their behavioral sensitization was additive. In addition, similar to the clinical situation in which the abuse potential of modafinil seems to be higher in female subjects, modafinil-induced locomotor sensitization had a higher magnitude in female mice. Supporting these behavioral sensitization data, modafinil produced a pronounced conditioned place preference in the mouse. Taken together, the present findings provide preclinical evidence for the addictive potential of modafinil. Our data also strongly suggest that similar neural substrates are involved in the psychomotor/rewarding effects of modafinil and cocaine.

ASSUNTO(S)

estimulantes do sistema nervoso central transtornos relacionados ao uso de substância cocaína/farmacologia camundongos farmacologia

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