Navegando por Palavras-chave "etanol"
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- ItemAcesso aberto (Open Access)Efeitos comportamentais e moleculares de fitocanabinoides em camundongos submetidos ao modelo da sensibilização locomotora induzida pelo etanol(Universidade Federal de São Paulo (UNIFESP), 2015-10-30) Filev, Renato [UNIFESP]; Mello, Luiz Eugenio Araujo de Moraes [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Drug dependence, including alcoholism, is a neuroadaptative process induced by mesolimbic dopaminergic pathway sensitization. Several neurochemical mechanisms increase the incentive salience of motivational agents, in our case, ethanol. This sensitization seems to play an important role on craving development, and when associated to cues or stress, could induce relapse. Experimental studies suggest that endocannabinoid system is involved on ethanol pharmacological effects and in the modulation of motivational circuit. Recently, we have found that rodents submitted to locomotor sensitization and then to 5 days of drug withdrawal show increased type 1 cannabinoid receptor (CB1) expression on prefrontal cortex and striatum. Furthermore, case reports and observational studies suggest Cannabis use to mitigate the problematic use of ethanol. Therefore,here we aimed to verify whether phytocannabinoids (CBD and THC) influence the maintenance of locomotor sensitization induced by ethanol. Additionally, we investigated CB1 receptor and c-Fos expression. CBD (2.5; 5.0; 10 and 50 mg/kg, i.p.) did not affect the maintenance of locomotor sensitization. On the other hand, there was a significant inhibitory effect of THC (2.5 mg/kg, i.p.) in this behavioral response, when administered alone or in conjunction with CBD (in a 1:1 proportion). THC did not change consistently c-Fos expression, but prevented CB1 receptor upregulation in the ventral striatum. Contrary to our hypothesis, there was no correlation between behavioral and molecular results. The behavioral results point to potential therapeutic effects of THC in alcoholism. THC/CBD association showed to be effective on the proposed model. Thus, as already recognized for the treatment of other human conditions, our findings bring new insights for the development of clinical trials using the association of THC/CBD in alcohol-related problems.
- ItemEmbargoEstudo da relação entre sensibilização comportamental ao etanol e estresse de restrição de movimentos: associação com níveis de corticosterona(Universidade Federal de São Paulo (UNIFESP), 2006-04-26) Trindade, Ágatha Asano [UNIFESP]; Souza-Formigoni, Maria Lucia Oliveira de [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)The relationship between drugs of abuse and stress has been demonstrated in several studies. On one hand, there are reports on cross sensitization between drugs of abuse and stressful evens. On the other hand, exposure to a stressor may induce sensitized behavioral response to a drug. Repeated administration of drugs may, however, induce a neuroendocrine sensitization of the hypothalamus-pituitaryadrenal axis (HPA) leading to a marked increase in the release of stress-related hormones. The objectives of the present study were to assess whether mice highly sensitized to the stimulant effect of ethanol presented high levels of corticosterone (CORT) after exposure to acute restraint stress (1 h) and whether an acute or repeated (7 days) exposure to this kind of stressor would affect the behavioral response to ethanol administration (acute and repeated). In the first experiment, mice were treated with 2.2 g/kg of ethanol or with saline and submitted to 1 h restraint stress. Blood samples were collected for determination of corticosterone (CORT) plasma levels. Exposure to stress increased CORT levels, but pre-treatment with ethanol or saline did not affect the hormone response. In Experiment 2, mice were first submitted to a 1 h restraint stress and 24 h later a 14-day treatment with ethanol or saline began. The pre-exposure to stress did not alter locomotor response to ethanol or saline, acute or repeatedly administered. On the 14th day of treatment, ethanol-treated mice presented higher CORT levels than saline-treated ones (p<0,05). In Experiment 3, mice were initially submitted to 1 h restraint stress for 7 days. After 24 h, the treatment with 2.2 g/kg of ethanol or saline started. Previous exposure to repeated (7 days) stress did not alter the mice’s locomotor response to ethanol or saline (acute or repeatedly administered). In a challenge carried out 4 days after the end of the treatment, ethanol-treated mice presented higher CORT levels than saline-treated ones (p<0,05). In addition, animals previously submitted to stress presented higher levels of CORT than non-stressed animals (p<0,05). These results suggest that sensitization to the stimulant effect of ethanol did not induce sensitization of the CORT response to restraint stress and that the acute or repeated exposure to restraint stress is not sufficient to alter the mice’s locomotor response to ethanol (acute or repeatedly). In summary, we did not observe cross sensitization between ethanol and 1 h restraint stress.
- ItemSomente MetadadadosExpressão do npy e do Δ fosb durante a abstinência em camundongos susceptíveis e resistentes à sensibilização locomotora induzida pelo etanol(Universidade Federal de São Paulo (UNIFESP), 2013-01-30) Pauli, Ricardo Fontao de [UNIFESP]; Silveira Filho, Dartiu Xavier da Silveira Filho [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Besides drug addiction, NPY is involved in anxiety-related behaviors, while FosB/ΔFosB plays a role in the resilience to stress and in the rewarding effects of drugs. Several studies in drug addiction have focused on the mechanisms associated with negative emotional state which emerges from withdrawal. We investigate how behavioral variability to develop ethanol-induced locomotor sensitization could change NPY and FosB/ΔFosB during withdrawal period. Methods: outbreed Swiss mice were daily treated with ethanol or saline for 21 days. According to the locomotor activity after the last ethanol injection, mice were classified as Sensitized (EtOH_High) or non-sensitized (EtOH_Low). After 18 hours or 5 days, their brains were processed for NPY and FosB/ΔFosB immunohistochemistry. Results: there were FosB/ΔFosB increases throughout withdrawal in the orbitofrontal cortex, striatum and dopaminergic mesencephalic nuclei, although in these two last the increases were higher in EtOH_Low. In contrast, increase on FosB/ΔFosB in the motor cortex was seen only in the EtOH_High. Regarding NPY, there were increases during ethanol withdrawal only in EtOH_High, and in the striatum, hippocampus, motor and piriform cortices. Interestingly, in the granular layer of dentate gyrus, increase in EtOH_High was seen only at 5 days of withdrawal. In contrast, in EtOH_Low group, there was an initial increase at 18 h of withdrawal, followed by decrease throughout withdrawal. Conclusion: NPY could contribute to the negative emotional states of withdrawal (given this prominent expression only in EtOH_High). In contrast, accumulation of FosB/ΔFosB could represent a compensatory mechanism to avoid these negative states (given this highest accumulation in EtOH_Low than EtOH_High).
- ItemAcesso aberto (Open Access)Posturografia estática em dependentes de drogas ilícitas e álcool(Associação Brasileira de Otorrinolaringologia e Cirurgia Cervicofacial, 2012-10-01) Moreira, Daniela Affonso; Ganança, Mauricio Malavasi [UNIFESP]; Caovilla, Heloisa Helena [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)The use of illicit drugs and alcohol can affect body balance. AIM: To evaluate balance control with static posturography in individuals addicted to illicit drugs, with or without alcohol abuse. Study design: Case-control, prospective. METHODS: 47 users of illicit drugs, with or without alcohol abuse, and a homogeneous control group consisting of 47 healthy individuals were submitted to a neurotological evaluation including Balance Rehabilitation Unit posturography. RESULTS: The stability threshold mean values were significantly lower (p < 0.0001) in users of illicit drugs, with or without alcohol abuse when compared to the control group; the mean values for sway velocity and ellipse area in all evaluated conditions were significantly higher (p <0.05) in the experimental group when compared to the control group, except for the ellipse area in static force surface and opened eyes (p = 0.168). CONCLUSION: The balance control of individuals addicted to illicit drugs with or without alcohol abuse could present stability threshold, sway velocity and ellipse area abnormalities in static posturography.