A retomada do consumo de etanol após abstinência é uma característica da dependência. O enriquecimento ambiental (EA) parece minimizar os efeitos de drogas de abuso, assim como a naltrexona (NTX). O estudo avaliou se EA, durante abstinência e associado ou não à NTX, alterou o consumo de etanol. Camundongos C57BL/6 foram expostos ao etanol 2h/dia. Após fase de aquisição, os animais foram separados em grupos. Os animais foram alojados em condições padrões e o outro em EA, 24h/dia ou 3h/dia. Após privação, os animais voltaram a ter acesso ao etanol semanalmente. Na última semana, tiveram acesso ao etanol por 24h e antes da reexposição foram submetidos ao estresse de contenção por 1h. Só neste caso, os grupos EA apresentaram uma redução no consumo de 24h. Ainda, outro experimento foi realizado associando o EA a baixas doses de NTX, mas não foram observadas alterações. Os resultados sugerem que o EA pode ajudar o animal a lidar melhor com o estresse, o que o protegeria de um comportamento de maior consumo de etanol. / The excessive ethanol consumption after abstinence is a feature of addiction. Environmental enrichment (EE) appears to minimize drug cravings, as well as naltrexone (NTX). The study evaluated whether EE during abstinence and with or without NTX, altered ethanol consumption. C57BL/6 mice were exposed to ethanol 2h/day. After an acquisition phase, mice were distributed into groups. The animals were housed in standard condition and the other in EE, 24h/day or 3h/day. After withdrawal, the animals returned to ethanol access weekly. On the last week, mice had access to ethanol for 24h and before re-exposure were subjected to restraint stress for 1h. EE groups decreased the ethanol consumption when mice had 24h free access to ethanol. Another experiment was performed with EE in association to low doses of NTX, but no differences in consumption were observed. The results suggests that EE may help the animal to cope better with stressful situations, resulting in blunted ethanol drinking.

A retomada do consumo de etanol após abstinência é uma característica da dependência. O enriquecimento ambiental (EA) parece minimizar os efeitos de drogas de abuso, assim como a naltrexona (NTX). O estudo avaliou se EA, durante abstinência e associado ou não à NTX, alterou o consumo de etanol. Camundongos C57BL/6 foram expostos ao etanol 2h/dia. Após fase de aquisição, os animais foram separados em grupos. Os animais foram alojados em condições padrões e o outro em EA, 24h/dia ou 3h/dia. Após privação, os animais voltaram a ter acesso ao etanol semanalmente. Na última semana, tiveram acesso ao etanol por 24h e antes da reexposição foram submetidos ao estresse de contenção por 1h. Só neste caso, os grupos EA apresentaram uma redução no consumo de 24h. Ainda, outro experimento foi realizado associando o EA a baixas doses de NTX, mas não foram observadas alterações. Os resultados sugerem que o EA pode ajudar o animal a lidar melhor com o estresse, o que o protegeria de um comportamento de maior consumo de etanol. / The excessive ethanol consumption after abstinence is a feature of addiction. Environmental enrichment (EE) appears to minimize drug cravings, as well as naltrexone (NTX). The study evaluated whether EE during abstinence and with or without NTX, altered ethanol consumption. C57BL/6 mice were exposed to ethanol 2h/day. After an acquisition phase, mice were distributed into groups. The animals were housed in standard condition and the other in EE, 24h/day or 3h/day. After withdrawal, the animals returned to ethanol access weekly. On the last week, mice had access to ethanol for 24h and before re-exposure were subjected to restraint stress for 1h. EE groups decreased the ethanol consumption when mice had 24h free access to ethanol. Another experiment was performed with EE in association to low doses of NTX, but no differences in consumption were observed. The results suggests that EE may help the animal to cope better with stressful situations, resulting in blunted ethanol drinking.

Álcool é substância lícita de abuso, promovendo dependência pela modulação de sistemas neurotransmissores, como GABAérgico e dopaminérgico. Taurina, um aminoácido utilizado como suplemento alimentar e constituinte de bebidas energéticas, exerce efeito modulatório positivo sobre receptores GABAA. Estudos em animais sugerem efeito terapêutico da taurina na síndrome de abstinência. No entanto, não se sabe o efeito da taurina sobre o comportamento de animais durante o uso de álcool. Portanto, o objetivo deste estudo foi avaliar o efeito do tratamento com taurina sobre o consumo voluntário de álcool e comportamentos de ratos. Foram oferecidas duas garrafas para ratos Wistar machos adultos, uma contendo álcool 20% em solução de sacarina 0,08% e a outra contendo apenas solução de sacarina 0,08% por 6 semanas. Ao grupo controle foram oferecidas duas garrafas contendo sacarina 0,08%. O consumo diário de líquidos dos dois grupos foi monitorado. No 22º dia eles foram divididos em 4 grupos (n=12/grupo) para receber taurina 100 mg/kg (grupos Álcool/TAU e Controle/TAU), via intraperitoneal, uma vez ao dia, por 19 dias, ou solução salina 0,9% (grupos Álcool/SAL e Controle/SAL). Nos dias 22 e 33, os ratos foram expostos ao teste de campo aberto e, no dia 34, ao teste de claro/escuro. Nossos resultados mostraram que o tratamento com taurina aumentou em mais de 10% a preferência por álcool em relação aos animais não tratados. O consumo de álcool médio no grupo Álcool/SAL foi 12 g/kg/dia, enquanto que no grupo Álcool/TAU foi 20 g/kg/dia, sendo que taurina aumentou significativamente o consumo a partir o sexto dia de tratamento. No campo aberto, dose aguda de taurina reduziu a ambulação total de animais controle, além de aumentar os cruzamentos centrais do grupo álcool. Taurina aguda e crônica aumentou a latência de auto-limpeza (grooming) e apenas o tratamento crônico reduziu 8 a frequência de grooming independentemente dos grupos. No teste de claro/escuro, taurina aumentou o tempo de permanência no compartimento claro, o número de transições entre os compartimentos e a latência para entrar no compartimento escuro apenas no grupo álcool, indicando efeito tipo-ansiolítico. Conclui-se que o tratamento crônico com taurina aumenta o consumo voluntário e preferência por álcool em ratos, possivelmente por efeito sinérgico com o álcool que facilita a ativação da via de recompensa dopaminérgica. O efeito tipo-ansiolítico da taurina no grupo álcool também pode ser justificado por efeito aditivo sobre receptores GABAA. Demonstramos que a taurina não apresenta efeito antiaditivo e, talvez, como o acamprosato, possa ser efetiva no controle da recaída, somente após abstinência. / Alcohol is a licit substance of abuse, promoting dependence by the modulation of different neurotransmitter systems, such as GABAergic and dopaminergic. Taurine, an amino acid used as food supplement and constituent of energy drinks, exerts positive modulatory effect on GABAA receptors. Animal studies suggest a therapeutic effect of taurine on withdrawal alcohol syndrome. However, the effect of taurine on the behavior of animals during alcohol use is not known. Therefore, the aim of this study was to evaluate the effect of taurine treatment on voluntary alcohol consumption and on behaviors of rats. Two bottles were offered to adult male Wistar rats, one containing 20% alcohol in 0.08% saccharin solution and another containing only 0.08% saccharin solution for 6 weeks. Two bottles containing 0.08% saccharin were offered to the control group. The daily liquid intake of both groups was monitored. On day 22 they were divided into 4 groups (n =12/group) to receive taurine 100 mg/kg (Alcohol/TAU and Control/TAU groups), intraperitoneally, once a day, for 19 days, or 0.9% saline (Alcohol/SAL and Control/SAL groups). On days 22 and 33, rats were exposed to the open field test and, on day 34, to the light/dark test. Our results showed that taurine treatment increased by more than 10% the alcohol preference compared to untreated animals. The average alcohol consumption in the Alcohol/SAL group was 12 g/kg/day, while in the Alcohol/TAU group it was 20 g/kg/day, and taurine significantly increased the consumption from the day 6 of treatment. In the open field, acute dose of taurine reduced the total ambulation of control animals and increased central crossings of alcohol group. Acute and chronic taurine increased the latency for grooming, and only chronic treatment reduced the frequency of grooming independently of the groups. On the light/dark test, taurine increased the time spent in light compartment, the number of 10 transitions between compartments and the latency to enter the dark compartment only in the alcohol group, indicating an anxiolytic-like effect. It is concluded that chronic taurine treatment increases alcohol voluntary consumption and preference in rats, possibly due to synergistic effects with alcohol that facilitates the activation of the dopaminergic reward pathway. The anxiolytic-like effect of taurine in the alcohol group may also be justified by additive effect on GABAA receptors. Our results show that taurine has no anti-additive effect and, perhaps as acamprosate, may be effective in controlling relapse only after abstinence.

Alcohol abuse disorders (AUD) represent a serious worldwide health problem with far reaching social, financial, and interpersonal implications. One of the most devastating facets of these disorders is the propensity to relapse following periods of abstinence. Ethanol withdrawal (EWD) is believed to promote relapse by increasing anxiety and craving, and may contribute to the development of cognitive decline associated with long-term dependence. Clinical data suggest that stress also plays a main role in both the development of AUD as well as relapse to drinking. As a physiological stressor, EtOH elevates levels of stress hormones (cortisol in humans, corticosterone (CORT) in the rat). Both CORT and EtOH have been shown to alter the composition, function, and activity of the N-methyl-D-aspartate (NMDA) receptor, and in particular, the NR2B subunit of this receptor. These alterations have been suggested to mediate EWD, which may negatively impact abstinence rates. This synergistic interaction between EtOH and CORT may present a therapeutic target for the treatment of EWD. In fact, data suggest that blocking the glucocorticoid receptor, which is a main target for CORT, with RU-486 could promote abstinence, as treatment with the drug has been shown to reduce consumption and the development dependence, as well as the severity of EWD and the cognitive deficits following EWD. However, these latter effects have not been validated in models of voluntary EtOH consumption. As there is considerable evidence that active versus passive intake can significantly impact neuroadaptations to ethanol this is an important consideration. These studies sought to characterize consumption and evaluate the development of dependence in a chronic voluntary model of intermittent access (IA) to EtOH. CORT plasma levels and protein expression of the glucocorticoid and NR2B receptors were measured during and/or following exposure. Finally, to assess the role of CORT in EtOH consumption and the development of dependence, the glucocorticoid receptor antagonist ORG-34517 was administered during access to EtOH. IA access to 20% EtOH produced varying levels of consumption (2.0-6.7g/kg/24hr exposure) and blood EtOH levels (6.3-116.9 mg/dl), but did not significantly affect food consumption or weight gain. Baseline CORT levels were found to be predictive of subsequent EtOH consumption and levels of consumption were sufficient to elevate CORT levels following one hour of EtOH exposure. Further, IA to EtOH was sufficient to produce dependence, as measured by elevations in the acoustic startle reflex following 26 hours and five days of withdrawal. No alteration in protein expression was observed regarding either the NR2B or glucocorticoid receptors and exposure to ORG-34517 had no effect on consumption or withdrawal.