Modafinil induces rapid-onset behavioral sensitization and cross-sensitization with cocaine in mice: implications for the addictive potential of modafinil

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)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.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 aro7FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIORFundação 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)2014/24277-4sem informaçãosem informaçã

Do Naps and Nocturnal Sleep Impact Gastroesophageal Reflux Disease Differently?

Universidade Federal de São Paulo, Dept Psicobiol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psicobiol, São Paulo, BrazilWeb of Scienc

Sleep Impairment: the Possible Link Between Childhood ADHD, Sensation Seeking, and Cocaine Dependence

AFIPCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo, São Paulo, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc

Assessment of tolerance to the effects of methamphetamine on daytime and nighttime activity evaluated with actigraphy in rhesus monkeys

Methamphetamine is one of the most largely consumed illicit drugs, and its use is associated with abuse liability and several adverse health effects, such as sleep impairment. Importantly, sleep quality can influence addiction treatment outcomes. Evidence suggests that tolerance can develop to the sleep-disrupting effects of stimulant drugs. The aim of the present study was to investigate the development of tolerance to the actigraphy-based sleep-disrupting and stimulant effects of methamphetamine self-administration in rhesus monkeys. Methamphetamine (0.03 mg/kg/inf, i.v.) self-administration was carried out following three different protocols: 14 consecutive days of self-administration, 5 days/week for 3 weeks, with a 2-day interval between 5-day blocks of self-administration, and 3 days/week for 3 weeks, with a 4-day interval between 3-day blocks of self-administration. Daytime activity and activity-based sleep measures were evaluated with Actiwatch monitors a week before (baseline parameters) and throughout each protocol. Methamphetamine self-administration markedly disrupted sleep-like measures and increased daytime activity. Tolerance developed to those effects with repeated methamphetamine intake exceeding five consecutive days. Inclusion of washout periods (2 or 4 days) between blocks of methamphetamine self-administration attenuated the development of tolerance, with longer breaks from methamphetamine intake being more effective in maintaining the sleep-disrupting and stimulant effects of methamphetamine. Tolerance can develop to the stimulant and sleep-disrupting effects of methamphetamine self-administration. Interruption of drug intake extends the effects of methamphetamine on sleep-like measures and daytime activity.USPHSAFIPFAPESPEmory Univ, Yerkes Natl Primate Res Ctr, 954 Gatewood Rd NE, Atlanta, GA 30329 USAUniv Fed São Paulo, Dept Psychobiol, R Napoleao Barros 925, BR-04021002 São Paulo, SP, BrazilEmory Univ, Dept Psychiat & Behav Sci, Yerkes Natl Primate Res Ctr, 954 Gatewood Rd NE, Atlanta, GA 30329 USAUniv Fed São Paulo, Dept Psychobiol, R Napoleao Barros 925, BR-04021002 São Paulo, SP, BrazilUSPHS: DA10344USPHS: DA031246USPHS: ODP51OD11132FAPESP: 2015/25482-3Web of Scienc

Treatment of cocaine addiction with amphetamine, a sleep-suppressant drug: associative learning, sleep patterns and clinical perspectives

Universidade Federal de São Paulo, Dept Psychobiol, BR-04021002 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychobiol, BR-04021002 São Paulo, BrazilWeb of Scienc

Relationships between sleep and addiction: the role of drug-environment conditioning

Addiction to cocaine and other amphetamine-like psychostimulants is a chronic relapsing disorder characterized by loss of control over drug taking. Sleep disturbance is common among patients in recovery from drug abuse and can precipitate relapse. It has been widely demonstrated that sleep deprivation and psychostimulants share similar neurobiological effects regarding the dopaminergic system. in addition, the persistence of a drug-environment conditioning induced by repeated psychostimulant treatment, which is deeply related to the dopaminergic neurotransmission, is thought to play a key role in the addictive cycle. in this scenario, we hypothesized that sleep deprivation is a potential detrimental factor to the extinction process of previously established drug-environment conditioning. Therefore, sleep deprivation would extend the pairing between the cocaine reinforcing effects and the environmental cues, thereby leading drug abusers to relapse. (C) 2014 Elsevier B.V. All rights reserved.Associacao Fundo de Incentivo a Pesquisa (AFIP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo, Dept Psychobiol, BR-04021002 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Pharmacol, BR-04021002 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychobiol, BR-04021002 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Pharmacol, BR-04021002 São Paulo, BrazilFAPESP: 2011/16580-0Web of Scienc