Navegando por Palavras-chave "Rhesus monkeys"

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    Assessment of tolerance to the effects of methamphetamine on daytime and nighttime activity evaluated with actigraphy in rhesus monkeys
    (Springer, 2017) Berro, Lais F. [UNIFESP]; Andersen, Monica L. [UNIFESP]; Howell, Leonard L.
    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.
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    Effects of the serotonin 2C receptor agonist WAY163909 on the abuse-related effects and mesolimbic dopamine neurochemistry induced by abused stimulants in rhesus monkeys
    (Springer, 2017) Berro, Lais F. [UNIFESP]; Diaz, Maylen Perez; Maltbie, Eric; Howell, Leonard L.
    Accumulating evidence shows that the serotonergic system plays a major role in psychostimulant abuse through its interactions with the dopaminergic system. Studies indicate that serotonin 5-HT2C receptors are one of the main classes of receptors involved in mediating the influence of serotonin in drug abuse. The aim of the present study was to evaluate the effects of the selective serotonin 5-HT2C receptor agonist WAY163909 on the behavioral neuropharmacology of cocaine and methamphetamine in adult rhesus macaques. Cocaine or methamphetamine self-administration and reinstatement were evaluated under second-order and fixed-ratio schedules of reinforcement, respectively. Cocaine- and methamphetamine-induced increases in dopamine were assessed through in vivo microdialysis targeting the nucleus accumbens. Pretreatment with WAY163909 dose-dependently attenuated cocaine and methamphetamine self-administration and drug-induced reinstatement of extinguished behavior previously maintained by cocaine or methamphetamine delivery. In an additional experiment, WAY163909 induced a dose-dependent attenuation of cocaine- or methamphetamine-induced dopamine overflow in the nucleus accumbens. Our data indicate that selective 5-HT2C receptor activation decreases drug intake and drug-seeking behavior in nonhuman primate models of psychostimulant abuse through neurochemical mechanisms involved in the modulation of mesolimbic dopamine.