title: Addictive potential of modafinil and cross-sensitization with cocaine: a pre-clinical study.
abstract: Repeated or even a single exposure to drugs of abuse can lead to 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. Male mice were used to investigate the ability of modafinil to induce locomotor sensitization after repeated or single administration in mice. Bidirectional cross-sensitization with cocaine and modafinil-induced conditioned place preference were also evaluated. Both repeated and single exposure to moderate and high doses of modafinil produced a pronounced locomotor sensitization that cross-sensitized in a bidirectional way with cocaine. Remarkably, when cocaine and modafinil were repeatedly administered sequentially, their behavioral sensitization was additive. Supporting these behavioral sensitization data, modafinil produced a pronounced conditioned place preference in the mouse. Taken together, the present findings provide pre-clinical 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.
authors.affiliation: Department of Pharmacology, Federal University of São Paulo, Brazil.
authors.forename: Raphael
authors.initials: R
authors.lastname: Wuo-Silva
authors.forename: Daniela F
authors.initials: DF
authors.lastname: Fukushiro
authors.forename: Aline R
authors.initials: AR
authors.lastname: Borçoi
authors.forename: Helaine A
authors.initials: HA
authors.lastname: Fernandes
authors.forename: Roberta
authors.initials: R
authors.lastname: Procópio-Souza
authors.forename: André W
authors.initials: AW
authors.lastname: Hollais
authors.forename: Renan
authors.initials: R
authors.lastname: Santos
authors.forename: Luciana T C
authors.initials: LT
authors.lastname: Ribeiro
authors.forename: Jussara M R M
authors.initials: JM
authors.lastname: Corrêa
authors.forename: Fernanda
authors.initials: F
authors.lastname: Talhati
authors.forename: Luis P
authors.initials: LP
authors.lastname: Saito
authors.forename: Tatiana C F
authors.initials: TC
authors.lastname: Aramini
authors.forename: Sonia R
authors.initials: SR
authors.lastname: Kameda
authors.forename: Lia R A
authors.initials: LR
authors.lastname: Bittencourt
authors.forename: Sergio
authors.initials: S
authors.lastname: Tufik
authors.forename: Roberto
authors.initials: R
authors.lastname: Frussa-Filho
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D059333:Central Nervous System Sensitization / Q000187:drug effects* / Q000502:physiology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D002755:Choice Behavior / Q000187:drug effects / Q000502:physiology; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000503:physiopathology*; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D000077408:Modafinil; D009042:Motivation / Q000187:drug effects / Q000502:physiology; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology*; D012201:Reward; D012931:Social Environment; D019966:Substance-Related Disorders / Q000503:physiopathology*
chemical_list: D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D003042:Cocaine; D000077408:Modafinil