Navegando por Palavras-chave "Reinstatement"

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    Dopamine transporter-related effects of modafinil in rhesus monkeys
    (Springer, 2010-06-01) Andersen, Monica L. [UNIFESP]; Kessler, Eileen; Murnane, Kevin S.; McClung, Jessica C.; Tufik, Sergio [UNIFESP]; Howell, Leonard L.; Emory Univ; Universidade Federal de São Paulo (UNIFESP)
    Modafinil is currently used as a treatment for daytime sleepiness.The objectives of this study were to explore the dopamine transporter (DAT)-related effects of modafinil on behavior and in vivo neurochemistry in rhesus monkeys (Macaca mulatta).The effects of modafinil (3.0-10 mg/kg, i.v.) were evaluated on locomotor activity, reinstatement of cocaine-maintained behavior, extracellular dopamine levels in the caudate nucleus, and DAT occupancy in the dorsal striatum. Eight subjects were fitted with a collar-mounted activity monitor to evaluate sleep-activity cycles, with 4 days of baseline recording preceding an injection of saline or modafinil (3.0-10 mg/kg). the effects of modafinil (3.0-10 mg/kg) and cocaine (0.3 mg/kg) on reinstatement of behavior that was previously maintained under a second-order schedule of i.v. cocaine delivery were tested in a separate group of subjects (n = 6). Finally, the effects of modafinil (3.0-10 mg/kg) on extracellular dopamine levels and DAT occupancy in vivo were characterized using microdialysis and positron emission tomography, respectively, in a within-subjects design (n = 4).Modafinil significantly increased nighttime locomotor activity and reinstated cocaine-maintained behavior but did not affect daytime locomotor activity. Modafinil significantly increased striatal extracellular dopamine levels at a dose that resulted in DAT occupancy of 64.4% (putamen) and 60.2% (caudate).The behavioral and in vivo dopaminergic effects of modafinil are consistent with the profile of a low potency DAT inhibitor and may indicate potential for abuse at high doses.
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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.