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BACKGROUND: The effects of tobacco smoke on the central nervous system are usually studied with isolated nicotine, ignoring other compounds present in cigarette smoke. The few studies that use in vivo whole-body cigarette smoke exposure are usually performed in expensive commercial apparatus. NEW METHOD: We presented a feasible, safe, and low-cost apparatus for cigarette smoke exposure in rodents. RESULTS: Rats exposed to cigarette smoke in this apparatus showed cotinine levels similar to human active smokers. Additional results showed that cigarette smoke exposure increased glutamate and aspartic acid levels and decreased leucine, isoleucine, ornithine, phenylalanine, and tryptophan levels in the cerebrospinal fluid of rats. COMPARISON WITH EXISTING METHOD(S): Our apparatus is feasible, safe, and costs 67-fold less than a commercial automatized smoking machine. Beyond the low cost, it does not require specialized knowledge for building or maintenance. CONCLUSIONS: We concluded that our low-cost apparatus is reliable and reproduces cigarette smoke use in humans.

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Copaiba oleoresin, extracted from the Copaifera reticulata tree, has been used as a remedy in popular medicine in the Brazilian Amazon for various purposes, including reducing drug abuse. Yet no studies evaluated the effect of repeated administration of copaiba oil on alcohol consumption in animals. To evaluate this effect, we divided adult male Wistar rats into a) an alcohol group in which the animals had free access to choose between two bottles: one containing alcohol solution (20%) and another containing vehicle solution (0.2% saccharin); and b) a control group with access to two bottles containing vehicle solution. Rats were free to drink 24 h per day, for 35 days. Daily alcohol consumption and weekly body weight gain and food intake were monitored. From day 22, half of the rats in each group received 600 mg kg-1 copaiba oleoresin and the other received vehicle, subcutaneously, once a day, for three days. On day 35, rats were evaluated in an open-field test. The results showed that copaiba oil decreased voluntary alcohol intake and preference between days 2 and 6 after the last administration. Copaiba treatment also decreased the food intake and body weight gain in both alcohol and control groups without changing behaviors in the open-field test. Therefore, copaiba oil was able to reduce voluntary alcohol consumption in rats and could be tested in humans as an adjuvant to treat alcohol use disorder.(AU)

O óleo extraído da árvore copaíba, Copaifera reticulata, tem sido usado na medicina popular na Amazônia brasileira para diversos fins, incluindo abuso de drogas. Contudo, não há estudos avaliando o efeito da administração repetida do óleo de copaíba sobre o consumo de álcool em animais. Para avaliar esse efeito, dividimos ratos Wistar machos adultos em dois grupos: a) um grupo álcool, no qual os animais tinham livre acesso a duas garrafas: uma contendo solução alcoólica (20%) e outra contendo solução veículo (sacarina 0,2%); e b) um grupo controle com acesso a duas garrafas contendo solução veículo. Os ratos podiam beber livremente, 24 horas por dia, durante 35 dias. O consumo diário de álcool, bem como o ganho de peso corporal semanal e a ingestão de alimentos foram monitorados. A partir do dia 22, metade dos ratos de cada grupo recebeu 600 mg kg-1 de óleo de copaíba e a outra metade recebeu veículo, por via subcutânea, uma vez ao dia, durante três dias. No dia 35, os ratos foram testados em teste de campo aberto. Os resultados mostraram que o óleo de copaíba diminuiu a ingestão voluntária e a preferência por álcool entre os dias 2 e 6 após a última administração. O tratamento com óleo de copaíba também diminuiu a ingestão alimentar e o ganho de peso corporal em ambos os grupos álcool e controle, sem alterar o comportamento no teste de campo aberto. Portanto, o óleo de copaíba foi capaz de reduzir o consumo voluntário de álcool em ratos e poderia ser testado em humanos como um adjuvante para tratar transtorno de uso de álcool.(AU)

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BACKGROUND: Red blood cells from smoking donors can have more lesions from oxidative stress, decreasing the benefits of blood transfusion. We aimed to explore the effect of cigarette smoking on the oxidative status of packed red blood cells (PRBCs) prior to storage. MATERIALS AND METHODS: We compared serum vitamin C, plasmatic malondialdehyde (MDA), and non-protein thiol groups (GSH) levels in PRBCs, as well glutathione peroxidase (GPx) and glutathione s-transferase (GST) activity in PRBCs from smoking (n=36) and non-smoking (n=36) donors. We also correlated urinary cotinine levels with these parameters. RESULTS: Cigarette smoking was associated with decreased serum levels of vitamin C and GPx, and increased GST activity in PRBCs. We found negative correlations between cotinine, GPx activity and vitamin C levels, and a positive correlation between cotinine and GST activity. DISCUSSION: Cigarette smoking changed antioxidant defences of PRBCs prior to storage and these parameters are correlated with cotinine levels. Increased RBC antioxidants such as GST may reflect an exposure to oxidants during erythropoiesis. Because of the inability of mature RBCs to resynthesise antioxidants, PRBCs from smokers may have higher risk of storage lesions than those from non-smoker donors.

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Interactions on neurotransmitter systems in the reward pathways may explain the high frequency of combined use of alcohol and cigarettes in humans. In this study, we evaluated some behavioral and neurochemical changes promoted by chronic exposure to alcohol and cigarette smoke in rats. Adult rats were administered with 2 g/kg alcohol (v.o.) or/and inhaled the smoke from 6 cigarettes, twice/day, for 30 days. Behavioral tests were performed 3 h after the alcohol administration and 1 h after the last exposure to cigarette smoke in the morning. Cerebrospinal fluid was collected for glutamate determination and the hippocampus was dissected for GABAA and NMDA receptor subunits mRNA expression determination. Results showed that the combined use of alcohol and cigarette smoke (ALTB) in rats increased the locomotor activity and all interventions decreased anxiety-like behaviors. Despite being on a short-term withdrawal, the cigarette smoke exposure decreased the percentage of open arm entries in the elevated plus maze test, which was prevented by combined use with alcohol. Even though GABAA and glutamate receptor subunits expression did not change in the hippocampus, glutamate levels were significantly higher in the cerebrospinal fluid from ALTB rats. Therefore, we showed that the combined use of alcohol and cigarette maintained a psychostimulant effect after a short-term withdrawal that was associated with the elevated glutamatergic activity. The combined use also prevented anxiety-like signs in cigarette smoke exposure rats, decreasing an adverse effect caused by nicotine withdrawal. These results could explain, in part, the elevated frequency of combined use of these two drugs of abuse in humans.

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Exposure to cigarette smoke and ethanol are proposed to trigger neurotoxicity, apoptosis, and to impair neuronal signaling. However, it is little known how the combination of both might trigger astrogliosis and the morphological changes capable of affecting a differential susceptibility of hippocampal regions to these licit drugs. The present study investigated the chronic effects of exposure to cigarette smoke and/or ethanol on behavioral parameters, apoptosis, and alteration in immunoreactivity of glial fibrillary acid protein (GFAP) and S100ß in the CA1, CA3, and dentate gyrus (DG) of the rat hippocampus. Adult male Wistar rats (n = 32) were divided into four groups: vehicle (VE, glucose 3% in water, 10 mL/kg), cigarette smoke (TOB, total 12 cigarettes per day), ethanol (ethanol, 2 g/kg), and cigarette smoke plus ethanol (TOB plus ethanol, total 12 cigarettes per day plus ethanol 2 g/kg) for 54 days. The groups were submitted to tail-flick, open-field, and inhibitory avoidance tasks. The results showed that ethanol per se worsened the short-term memory. The association between TOB and ethanol increased the immunoreactivity of cleaved caspase-3 in the CA3 and DG regions. The TOB plus ethanol group showed a lower immunoreactivity to GFAP in all regions of the hippocampus. In addition, ethanol and TOB per se also reduced the immunoreactivity for GFAP in the DG. Ethanol increased S100ß immunoreactivity only in the DG. In conclusion, this study showed that only ethanol worsened short-term memory, and the DG became more susceptible to changes in the markers investigated. This evidence suggests that DG is more sensitive to neurotoxicity induced by cigarette smoke and ethanol.

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Devastating effects of exposure to alcohol and tobacco smoke on health are extensively reported in the literature. However, few studies have attempted to elucidate the consequences of their combined use on the central nervous system. Here we studied the effect of this combined use on some oxidative, inflammatory, and neurotrophic parameters in the hippocampus, striatum, and frontal cortex of rats. Adult Wistar rats were allocated into control (CT), alcohol (AL), tobacco smoke (TB), or combined (ALTB) groups. Rats were exposed to environmental air (CT and AL groups) or to the smoke from six cigarettes (TB and ALTB groups) immediately after tap water (CT and TB) or 2 g of alcohol/kg (AL and ALTB) oral gavage administration, twice a day, for 4 weeks. On day 28, rats were euthanized and areas of the brain were dissected to evaluate some cellular redox parameters, pro-inflammatory cytokine levels, and brain-derived neurotrophic factor (BDNF) levels. A one-way analysis of variance showed that the ALTB combined treatment significantly increased oxidative stress levels in the hippocampus. ALTB also increased interleukin-1ß levels in the striatum and frontal cortex and tumoral necrosis factor-α levels in the frontal cortex compared with those of AL, TB, and CT rats. Combined treatment also decreased the BDNF levels in the frontal cortex of rats. Oxidative damage was found, more importantly, in the hippocampus, and inflammatory parameters were extended to all areas of the brain that were studied. Our results showed an interaction between alcohol and tobacco smoke according to the area of the brain, suggesting an additional risk of neural damage in alcoholics who smoke.

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Alcoholism has been characterized as a systemic pro-inflammatory condition and alcohol withdrawal has been linked to various changes in the brain homeostasis, including oxidative stress and glutamate hyperactivity. N-acetylcysteine (NAC) is an anti-inflammatory and antioxidant multi-target drug with promising results in psychiatry, including drug addiction. We assessed the effects of NAC on the serum and brain inflammatory cytokines after cessation of chronic alcohol treatment in rats. Male Wistar rats received 2 g/kg alcohol or vehicle twice a day by oral gavage for 30 days. Rats were treated, from day 31 to 34, with NAC (60 or 90 mg/kg) or saline, intraperitoneally, once daily. Rats were sacrificed at day 35, trunk blood was collected and the frontal cortex and hippocampus dissected for assessment of TNF-α, IL-1ß, IL-6, IL-18, IL-10. NAC prevented the increase of pro-inflammatory cytokines and the decrease of anti-inflammatory cytokine in the frontal cortex and hippocampus. No changes were observed on serum cytokines. We conclude that NAC protects against inflammation induced by chronic (30 days) alcohol ingestion followed by 5 days cessation in two rat brain areas. Because inflammation has been documented and associated with craving and relapse in alcoholics, the data revealed by this study points to the validity of NAC clinical evaluation in the context of alcohol detoxification and withdrawal.

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