Navegando por Palavras-chave "Methamphetamine"

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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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    Behavioral changes and brain energy metabolism dysfunction in rats treated with methamphetamine or dextroamphetamine
    (Elsevier B.V., 2012-11-14) Feier, Gustavo; Valvassori, Samira S.; Lopes-Borges, Jessica; Varela, Roger B.; Bavaresco, Daniela V.; Scaini, Giselli; Morais, Meline O.; Andersen, Monica L. [UNIFESP]; Streck, Emilio L.; Quevedo, Joao; Univ So Santa Catarina; Universidade Federal de São Paulo (UNIFESP)
    Studies have demonstrated that AMPHs produce long-term damage to the brain dopaminergic, serotoninergic and glutamatergic regions. Prefrontal cortex, amygdala, hippocampus and striatum appear to be involved in the toxicity and behavioral changes induced by AMPHs. A single dose of AMPH causes mitochondrial dysfunction and oxidative stress in rat brain. the goal of the present study was thus to investigate the potency of two amphetamines, dextroamphetamine (d-AMPH) and methamphetamine (m-AMPH), on the behavior and energetic dysfunction in the brain of rats. d-AMPH and m-AMPH increased the crossing and rearing behaviors. the numbers of visits to the center were increased by d-AMPH and m-AMPH only at 2 mg/kg. Likewise, at a high dose (2 mg/kg), the injection of m-AMPH increased the amount of sniffing. the AMPHs significantly decreased the activities of Krebs cycle enzymes (citrate synthase and succinate dehydrogenase) and mitochondrial respiratory chain complexes (I-IV); nevertheless, this effect varied depending on the brain region evaluated. in summary, this study demonstrated that at high doses, m-AMPH, increased stereotyped (sniffing) behavior in rats, but d-AMPH did not. However, this study shows that d-AMPH and m-AMPH seem to have similar effects on the brains energetic metabolism. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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    Differences between dextroamphetamine and methamphetamine: behavioral changes and oxidative damage in brain of Wistar rats
    (Springer, 2012-01-01) da-Rosa, Dayane D.; Valvassori, Samira S.; Steckert, Amanda V.; Arent, Camila O.; Ferreira, Camila L.; Lopes-Borges, Jessica; Varela, Roger B.; Mariot, Edemilson; Dal-Pizzol, Felipe; Andersen, Monica L. [UNIFESP]; Quevedo, Joao; Univ Extremo Catarinense; Univ So Santa Catarina; Universidade Federal de São Paulo (UNIFESP)
    In this study methamphetamine (m-AMPH) and dextroamphetamine (d-AMPH) were compared to determine the potency of the two drugs on behavior and oxidative damage in brain of rats. Male adult Wistar rats were given single (acute administration) or repeated (chronic administration, 14 days) intraperitoneal injections of saline (0.9% NaCl), d-AMPH (2 mg/kg) or m-AMPH (0.25, 0.5, 1 or 2 mg/kg). Locomotor activity was evaluated in open-field apparatus 2 h after the last drug injection. Additionally, thiobarbituric acid reactive substances (TBARS) and protein carbonyl formation were measured in the prefrontal cortex, amygdala, hippocampus and striatum. in both experiments, d-AMPH and m-AMPH (all doses administered) increased the locomotor activity of animals, meantime, no significant difference between d-AMPH and m-AMPH was observed. d-AMPH and m-AMPH increased lipid and protein damage, but m-AMPH was more potent than d-AMPH, however, this effect varies depending on the brain region and the experimental protocol. the results of this study show that d-AMPH and m-AMPH have similar behavioral effects, which previous studies had already reported. On the other hand, this study demonstrated that the m-AMPH induces oxidative damage greater than d-AMPH, showing neurochemical differences previously unknown.
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    Efeito da inativação farmacológica da amídala na sensibilização contexto- específico induzida por metanfetamina em ratos
    (Universidade Federal de São Paulo (UNIFESP), 2020-06-25) Perillo, Mayara Gomes [UNIFESP]; Cruz, Fabio Cardoso [UNIFESP]; Universidade Federal de São Paulo
    The amygdaloid complex, in particular, the basolateral and central, are considered structures related to associative learning processes related to negative and positive stimuli. Drug addiction involves associative learning behaviors. Repeated drug abuse use, leads the individual to associate the effect of the drug with environmental stimuli where the substance is consumed. And during this use, only the exposure to environmental cues can trigger drug craving. The compulsion triggered by cues is due to the sensitization of the mesocorticolimbic pathway, which increases the salience of drug-associated stimuli. This theory is called behavioral sensitization that in rodents can be studied using the locomotor sensitization model. This phenomenon is characterized by the gradual increase in locomotor activity in response to repeated administration of a drug. Locomotor sensitization is more robust when the substance is administered repeatedly in the same context. This type of sensitization is called context-specific. This study aimed to investigate the effect of pharmacological inactivation of basolateral amygdala on methamphetamine-induced context-specific sensitization in rats. For this, distinct groups of male Wistar rats were sensitized for seven days with different doses of methamphetamine in two different contexts (Context A or B). Seven days after the last sensitization session, the animals received methamphetamine or saline injection, and the locomotor activity was evaluated for 45 minutes in the context A. Our results showed that the repeated methamphetamine administration at the dose of 1 mg/kg was able to develop context-specific sensitization. Sensitized animals showed a decreased neuronal activity in basolateral amygdala induced by methamphetamine administration. Finally, we observed that inhibition of basolateral amygdala enhanced expression of context-specific sensitization in rats. Taken together, these results indicate the participation of the basolateral amygdala in neuroplasticities related to drug addiction.
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    Effects of cocaine, methamphetamine and modafinil challenge on sleep rebound after paradoxical sleep deprivation in rats
    (Associação Brasileira de Divulgação Científica, 2008-01-01) Martins, Raquel Cristina Silva [UNIFESP]; Andersen, Monica Levy [UNIFESP]; Shih, Ming Chi [UNIFESP]; Tufik, Sergio [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Sleep loss is both common and critically relevant to our society and might lead to the abuse of psychostimulants such as amphetamines, cocaine and modafinil. Since psychoactive substance abuse often occurs within a scenario of sleep deficit, the purpose of this investigation was to compare the sleep patterns of rats challenged with cocaine (7 mg/kg, ip), methamphetamine (7 mg/kg, ip), or modafinil (100 mg/kg, ip) subsequent to paradoxical sleep deprivation (PSD) for 96 h. Our results show that, immediately after 96 h of PSD, rats (10 per group) that were injected with a psychostimulant presented lower percentages of paradoxical sleep compared to those injected with saline (P < 0.01). Regarding slow wave sleep (SWS), rats injected with psychostimulants after PSD presented a late rebound (on the second night subsequent to the injection) in the percentage of this phase of sleep when compared to PSD rats injected with saline (P < 0.05). In addition, the current study has produced evidence of the characteristic effect of each drug on sleep architecture. Home cage control rats injected with modafinil and methamphetamine showed a reduction in SWS compared with the saline group. Methamphetamine affected sleep patterns most, since it significantly reduced paradoxical sleep, SWS and sleep efficiency before and after PSD compared to control (P < 0.05). Cocaine was the psychostimulant causing the least changes in sleep pattern in relation to those observed after saline injection. Therefore, our results suggest that abuse of these psychostimulants in a PSD paradigm aggravates their impact on sleep patterns.
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    Effects of lithium and valproate on oxidative stress and behavioral changes induced by administration of m-AMPH
    (Elsevier B.V., 2012-08-15) da-Rosa, Dayane D.; Valvassori, Samira S.; Steckert, Amanda V.; Ornell, Felipe; Ferreira, Camila L.; Lopes-Borges, Jessica; Varela, Roger B.; Dal-Pizzol, Felipe; Andersen, Monica L. [UNIFESP]; Quevedo, Joao; Univ So Santa Catarina; Universidade Federal de São Paulo (UNIFESP)
    In the last years our research group has studied and validated the animal model of mania induced by dextroamphetamine (D-AMPH). Considering the lack of animal models of mania reported in the literature; this study evaluated the possibilities to validate the animal model induced by methamphetamine (m-AMPH). Then, we evaluated the effects of lithium (Li), valproate (VPA) on the behavior and parameters of oxidative damage in rat brain after administration of m-AMPH. in the prevention treatment, Wistar rats were pretreated with Li. VPA or saline (Sal) for 14 days, and then, between days 8 and 14, rats were treated with m-AMPH (1, 0.5 or 0.25 mg/kg) or Sal. in the reversal treatment, rats were first given m-AMPH (0.25 mg/kg) or Sal. Locomotor behavior was assessed using the open-field task and parameters of oxidative damage were measured in brain structures. Our results show that the hyperactivity was prevented and reverted by Li and VPA only when m-AMPH was administered in the dose of 0.25 mg/kg. in addition, the m-AMPH in all doses administrated induced oxidative damage in both structures tested in two models. Li and VPA reversed and prevented this impairment, however in a way dependent of cerebral area, the dose of m-AMPH and technique. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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    Effects of methamphetamine self-administration on actigraphy-based sleep parameters in rhesus monkeys
    (Springer, 2013-05-01) Andersen, Monica L. [UNIFESP]; Diaz, Maylen P.; Murnane, Kevin S.; Howell, Leonard L.; Emory Univ; Universidade Federal de São Paulo (UNIFESP)
    Sleep disorders and substance abuse are highly comorbid. Although methamphetamine is a very commonly abused drug, to the best of our knowledge, no study has evaluated its effects on sleep during drug use and abstinence under well-controlled conditions in laboratory animals.The objective of this study was to examine the effects of methamphetamine self-administration on sleep-like measures in nonhuman primates.Adult male rhesus monkeys (Macaca mulatta; n = 4) self-administered methamphetamine (0.01 and 0.03 mg/kg/injection, i.v.) under a fixed-ratio 20 schedule of reinforcement (60-min sessions once a day, 5 days per week) for 5 weeks. Sleep-like measures were evaluated with Actiwatch monitors before, during, and after each period of drug self-administration.Both doses of methamphetamine reliably maintained self-administration. Methamphetamine (0.03 mg/kg) increased derived measures of latency to sleep onset and sleep fragmentation, and decreased sleep efficiency compared to abstinence, and higher methamphetamine intake predicted worse sleep quality. However, sleep normalized immediately after the discontinuation of methamphetamine self-administration.Methamphetamine markedly disrupted sleep-like measures; however, methamphetamine self-administration did not disrupt sleep quality during subsequent periods of drug abstinence.
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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.
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    Facilitation of ejaculation after methamphetamine administration in paradoxical sleep deprived rats
    (Elsevier B.V., 2003-07-18) Andersen, Monica Levy [UNIFESP]; Bignotto, Magda [UNIFESP]; Tufik, Sergio [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    This study investigated the effects of methamphetamine (MA) on genital reflexes in paradoxical sleep deprived (PSD) rats. Different doses of MA (0, 4. 16 and 64 mg/kg) were acutely given after PSD or the equivalent time to control animals. We observed enhancement of spontaneous ejaculation in PSD rats with larger doses of MA, the highest of which induced ejaculation in 100% of the PSD rats. This was significantly higher than the 30% in the control. Although testosterone exerts motivational effects on male sexual behavior, our data shows that testosterone levels were lower after the PSD period in saline and in the 64 mg/kg MA groups, which present ejaculation at different rates (20% and 100%, respectively). Progesterone levels were significantly higher in PSD-saline in relation to control group and in the 16 and 64 mg/kg of MA groups compared to the other doses. Since PSD induces dopaminergic alterations and dopamine (DA) has a key role in male sexual behavior, plasma DA was also measured. the DA concentration was enhanced in all PSD groups compared with their control group. the mechanism that activates steroid hormones may represent an important physiological effect through which neurotransmitters can affect behavioral events. These data show that MA facilitates ejaculation in PSD rats, however, further studies need to be carried out in order to clarify the hormonal-neurochemical mechanisms involved. (C) 2003 Elsevier Science B.V. All rights reserved.
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    Fatores envolvidos no desenvolvimento e expressão da sensibilização comportamental ao efeito estimulante do modafinil e metanfetamina
    (Universidade Federal de São Paulo (UNIFESP), 2010-04-28) Soeiro, Aline da Costa [UNIFESP]; Oliveira, Maria Gabriela Menezes de [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    The behavioral sensitization refers to the progressive increase of the stimulatory effect induced by repeated administration of drugs of abuse such as cocaine and amphetamine. Previous studies suggest that the environment paired with the drug stimulant effect of those drugs has an important role in the behavioral sensitization phenomena. Besides, the chronic treatment with one drug of abuse can induce a different patter of response to the administration of other drug indicating that both drug share some similar mechanism of action. The present study aimed to investigate the involvement of contextual learning in the modafinil and methamphetamine behavioral sensitization phenomena and if there is cross-sensitization between the two drugs. Fifteen days after the contextual fear conditioning task, mice received repeated administration of vehicle or modafinil (50mg/kg - Experiment 2) and saline or methamphetamine (1mg/kg - Experiment 3) for 10 days; they were tested in activity cages on days 1, 5 and 10. To evaluate the expression of behavioral sensitization the mice were challenged with vehicle or modafinil (50mg/kg - Experiment 2) and saline or methamphetamine (1 mg/kg - Experiment 3) and then they were tested in the activity cages and in the open field arena. For cross-sensitization test, mice from Experiment 2 were challenged with saline and methamphetamine (1mg/kg) and those mice from Experiment 3 were challenged with vehicle and modafinil (50mg/kg). In both experiments we did not find any correlation between the levels of freezing in the contextual fear conditioning task and different levels of sensitization. Modafinil-sensitized subgroup of mice expressed clear behavioral sensitization in the activity cage, but not in the open field, suggesting a context-dependent expression of modafinil sensitization. We also observed a symmetric cross-sensitization between modafinil and methamphetamine. Our findings indicate that there are a important individual variability to the development of behavioral sensitization to methamphetamine and to modafinil. Besides, we suggest that modafinil and methamphetamine seem to share similar mechanisms of action.
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    GABA(A) receptor positive allosteric modulators modify the abuse-related behavioral and neurochemical effects of methamphetamine, in rhesus monkeys
    (Pergamon-Elsevier Science Ltd, 2017) Berro, Lais F. [UNIFESP]; Andersen, Monica L. [UNIFESP]; Tufik, Sergio [UNIFESP]; Howell, Leonard L.
    GABA(A) receptor positive allosteric modulators (GABA(A) receptor modulators) are commonly used for the treatment of insomnia. Nevertheless, the effects of these compounds on psychostimulant-induced sleep impairment are poorly understood. Because GABA(A) receptor modulators have been shown to decrease the abuse-related effects of psychostimulants, the aim of the present study was to evaluate the effects of temazepam (0.3, 1.0 or 3.0 mg/kg) and eszopiclone (0.3, 1.0 or 3.0 mg/kg), two GABA(A) receptor modulators, on the behavioral neuropharmacology of methamphetamine in adult rhesus macaques (n = 5). Sleep-like measures and general daytime activity were evaluated with Actiwatch monitors. Methamphetamine self-administration (0.03 mg/kg/inf) was evaluated during morning sessions. Methamphetamine-induced dopamine overflow was assessed through in vivo microdialysis targeting the nucleus accumbens. Nighttime treatment with either temazepam or eszopiclone was ineffective in improving sleep-like measures disrupted by methamphetamine self-administration. Acute pretreatment with a low dose of temazepam before self-administration sessions increased methamphetamine self administration without affecting normal daytime home-cage activity. At a high dose, acute temazepam pretreatment decreased methamphetamine self-administration and attenuated methamphetamine-induced increases in dopamine in the nucleus accumbens, without decreasing general daytime activity. Acute eszopiclone treatment exerted no effects on methamphetamine intake or drug-induced increases in dopamine. Our study suggests that treatments based on GABA(A) receptor modulators are not effective for the treatment of sleep disruption in the context of psychostimulant use. In addition, distinct GABA(A) receptor modulators differentially modulated the abuse-related effects of methamphetamine, with acute treatment with the high efficacy GABA(A) receptor modulator temazepam decreasing the behavioral and neurochemical effects of methamphetamine. (C) 2017 Elsevier Ltd. All rights reserved.
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    Individual differences to repeated ethanol administration may predict locomotor response to other drugs, and vice versa
    (Elsevier B.V., 2009-02-11) Abrahao, Karina Possa [UNIFESP]; Hartmann Quadros, Isabel Marian [UNIFESP]; Oliveira Souza-Formigoni, Maria Lucia [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Repeated administration of drugs may induce adaptations which affect the behavioral responses to the drug itself or to other drugs. Whether individual characteristics to repeated drug administration predict sensitivity to the effects of another drug is not clear. We evaluated whether or not mice that present higher vs. lower locomotor response after repeated treatment with ethanol display increased or decreased locomotor responses when challenged with methamphetamine or morphine, and vice versa. Mice received daily i.p. 2.2 g/kg ethanol (21 days), 1.0 mg/kg methamphetamine or 10 mg/kg morphine (10 days). According to the response presented during repeated drug treatment, mice were classified as HIGH or LOW activity groups. Locomotor activity was monitored after mice were challenged with saline, and 48 h later with a drug. Ethanol-treated mice were challenged with methamphetamine or morphine, methamphetamine- and morphine-treated animals were challenged with ethanol. After repeated treatment with ethanol or methamphetamine, locomotor sensitization was observed only in HIGH mice, not LOW mice. Ethanol-treated mice with HIGH activity showed sensitized, increased locomotor responses to methamphetamine (p<0.05), but not to morphine. Locomotor responses to ethanol were not affected by a previous history of methamphetamine treatment. Although repeated administration of morphine failed to induce sensitization, morphine-treated mice with HIGH activity presented sensitized locomotor responses after an ethanol challenge. the current experiments confirm important individual differences in response to repeated administration of ethanol, methamphetamine and morphine, which in some cases affected the locomotor response to a second drug challenge, in an asymmetrical pattern. (C) 2008 Elsevier B.V. All rights reserved.
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    Investigação dos mecanismos envolvidos nos efeitos comportamentais da metanfetamina relacionados ao sono e à dependência química em macacos rhesus
    (Universidade Federal de São Paulo (UNIFESP), 2017-02-28) Berro, Laís Fernanda [UNIFESP]; Andersen, Monica Levy [UNIFESP]; Sergio Tufik [UNIFESP]; http://lattes.cnpq.br/1375290481822767; http://lattes.cnpq.br/4951931552005515; http://lattes.cnpq.br/4991756102121358; Universidade Federal de São Paulo (UNIFESP)
    Sleep disorders and substance abuse are highly comorbid. The GABAergic and serotonergic systems participate in the regulation of both drug addiction and sleep-wake cycle. The aim of the present study was to evaluate the mechanisms underlying the abuse- and sleep-related behavioral effects of methamphetamine (METH) in rhesus monkeys. Our results show that METH disrupts sleep on the first day of self-administration, and that in the absence of the drug and of drug-associated cues (extinction), the sleep condition is restored to baseline levels. The reintroduction of drug-conditioned cues during effective reinstatement sessions induced sleep disruption. Tolerance can develop to the sleep-disrupting and locomotor stimulant effects of METH if self-administration sessions exceed 5 consecutive days, effect that is attenuated by the inclusion of washout periods between self-administration blocks. Treatment with the GABAA receptor modulator temazepam at a high dose attenuated METH self-administration and METH-induced dopamine overflow in the nucleus accumbens (NAc). The GABAA receptor modulator eszopiclone exerted did not alter METH effects. Moreover, treatments based on GABAA receptor modulators were not effective in improving sleep measures disrupted by METH. Night treatment with the selective 5-HT2C receptor agonist WAY163909, on the other hand, was effective in attenuating the effects of METH on sleep. WAY163909 also attenuated METH intake, METH-induced reinstatement and METH-induced dopamine overflow in the NAc. Extending those findings to another psychostimulant, WAY163909 also attenuated the abuse-related behavioral and neurochemical effects of cocaine. Our findings suggest that serotonin 5-HT2C receptors agonists are effective in reversing the behavioral and neurochemical effects of psychostimulants, being more selective than GABAA receptor modulators.