UChB Rats Research Articles

P-05SIMULTANEOUS INTAKE OF ETHANOL AND CAFFEINE ON APOPTOSIS IN THE CEREBELLUM OF UChB RATS (VOLUNTARY ETHANOL CONSUMERS): MIcroRNAs AND GENE EXPRESSIONS

The combination of ethanol with caffeine by consuming “energy drinks” is becoming increasingly popular among young people. The work showed the effects of simultaneous use of ethanol and caffeine on apoptosis in the cerebellum of UChB rats. The adult rats …

PPARα Agonists Reduce Alcohol Drinking: Do They Act in the Brain or in the Liver?

There are good news for the alcohol field. In the past few years, peroxisome proliferator-activator drugs were reported to reduce voluntary alcohol intake in animal models. Barson et al. (2009) showed that gemfibrozil reduced alcohol drinking in rats. Recently, similar results were obtained with fenofibrate in high-alcohol-drinker UChB rats (Karahanian et al. , 2014) and mice (Blednov et al. , 2015). Moreover, a phase 2 clinical trial led by Barbara Mason (The Scripps Research Institute) was started to test the hypothesis that alcohol-dependent subjects treated with fenofibrate will report decreased craving for alcohol following cue-exposure and will report less drinking post treatment (clinicaltrials.gov/ct2/show/NCT02158273). The peroxisome proliferator-activated receptors (PPARs) are transcription factors (nuclear receptors) that play essential roles in the regulation of cellular differentiation, development and metabolism. Three types of PPARs have been identified: alpha, gamma and beta/delta. PPARα is the most abundant isoform in the liver; PPARβ/δ is expressed ubiquitously in all tissues; and PPARγ is expressed mainly in adipose tissue. PPARα is activated by natural ligands (some types of fatty acids) and by synthetic agonists such as fibrate drugs (clofibrate, gemfibrozil, ciprofibrate, bezafibrate and fenofibrate). Fibrates are widely used in the clinic for the treatment of high blood-triglyceride levels. The mechanisms by which PPARα agonists are effective in reducing alcohol consumption are not fully understood. Currently, there are two views: (a) fibrates would act in the brain, changing the expression of genes …

(R)-Salsolinol, a product of ethanol metabolism, stereospecifically induces behavioral sensitization and leads to excessive alcohol intake.

Ethanol is oxidized in the brain to acetaldehyde, which can condense with dopamine to generate (R/S)-salsolinol [(RS)-SAL]. Racemic salsolinol [(RS)-SAL] is self-infused by rats into the posterior ventral tegmental area (VTA) at significantly lower concentrations than those of acetaldehyde, suggesting that (RS)-SAL is a most active product of ethanol metabolism. Early studies showed that repeated intraperitoneal or intra-VTA administration of (RS)-SAL (10 mg/kg) induced conditioned place preference, led to locomotor sensitization and increased voluntary ethanol consumption. In the present study, we separated the (R)- and (S)-enantiomers from a commercial (RS)-SAL using a high-performance liquid chromatography with electrochemical detection system fitted with a β-cyclodextrin-modified column. We injected (R)-SAL or (S)-SAL (30 pmol/1.0 μl) into the VTA of naïve UChB rats bred as alcohol drinkers to study whether one or both SAL enantiomers are responsible for the motivated behavioral effects, sensitization and increase in voluntary ethanol intake. The present results show that repeated administration of (R)-SAL leads to (1) conditioned place preference; (2) locomotor sensitization; and (3) marked increases in binge-like ethanol intake. Conversely, (S)-SAL did not influence any of these parameters. Overall, data indicate that (R)-SAL stereospecifically induces motivational effects, behavioral sensitization and increases ethanol intake.

Testosterone therapy differently regulates the anti- and pro-inflammatory cytokines in the plasma and prostate of rats submitted to chronic ethanol consumption (UChB).

Ethanol consumption damages the prostate, and testosterone is known by anti-inflammatory role. The cytokines were investigated in the plasma and ventral prostate of UChB rats submitted or not to testosterone therapy by ELISA and Western blot, respectively. Additionally, inflammatory foci and mast cells were identified in the ventral prostate slides stained by hematoxylin and eosin and toluidine blue, respectively. Inflammatory foci were found in the ethanol-treated animals and absent after testosterone therapy. Plasma levels of IL-6 and IL-10 were not changed while TNFα and TFG-β1 were increased in the animals submitted testosterone therapy. Regarding to ventral prostate, IL-6 did not alter, while IL-10, TNFα, and TFG-β1 were increased after testosterone therapy. Ethanol increases NFR2 in addition to high number of intact and degranulated mast cell which were reduced after testosterone therapy. So, ethanol and testosterone differentially modulates the cytokines in the plasma and prostate.

Interaction of maternal separation on the UCh rat Cerebellum

Maternal care is the main source of signals and stimuli for proper development, growth, and production of adjustment responses to stressful factors. Adverse experiences in childhood are associated with a vulnerability to developing abusive ethanol ingestion via alterations of the response of the hypothalamic-pituitary-adrenal axis. Alcoholism causes global brain abnormalities, with the cerebellum being one of the most susceptible areas. We evaluated the effect of maternal separation on the cerebellum structure of male UCh rats. Adult male UChA (low 10% ethanol consumption) and UChB (high 10% ethanol consumption) rats were divided in to four experimental groups: (1) UChA, (2) UChA maternal separation (MS), (3) UChB, and (4) UChB MS. The MS occurred between the 4th and 14th days of age, for 240 min day(-1) . Euthanasia was performed at 120 days of age. An image analysis system was used to measure cerebellar cortical height and Purkinje cellular area and height in five rats from each group. The cerebellar sections were stained with antibodies against IGFR-I. MS did not alter the ethanol consumption of UChA and UChB rats. Corticosterone level was significantly higher in UChA MS and UChB MS rats than in UChA and UChB rats. The Purkinje cellular area and height were higher in UChA MS rats. IGFR-I expression was observed in the cortical glomerular area of UChA MS and UChB MS rats. MS altered the Purkinje cells in the cerebella of male UCh rats.

Varenicline and cytisine: two nicotinic acetylcholine receptor ligands reduce ethanol intake in University of Chile bibulous rats

Neuronal nicotinic acetylcholine receptors (nAChRs) are pharmacological targets that have recently been implicated in the reinforcing effects of many drugs of abuse, including ethanol. Varenicline and cytisine are nAChR partial agonists in clinical use as smoking cessation aids. However, their efficacies to reduce alcohol consumption have not been fully studied. This study aims to compare the effects of varenicline and cytisine on ethanol consumption by rats bred for many generations as high ethanol drinkers (UChB). Repeated dosing (0.5 or 1.0mg/kg/day i.p.) of varenicline or cytisine, for three consecutive days, to male UChB rats pre-exposed to 10% (v/v) ethanol and water 24h/day for 4weeks, significantly reduced alcohol intake and preference of ethanol over water during 1- and 24-h ethanol access periods. This effect was specific for ethanol intake and was not observed for 0.2% saccharin or water consumption. Varenicline appears to be more effective than cytisine, probably due to its more favorable pharmacokinetic and pharmacodynamic properties. Long-term use of both nAChRs ligands for more than 8-10days induced tolerance to their effects on ethanol consumption. This preclinical study in UChB rats demonstrated that both varenicline and cytisine reduce alcohol intake, with varenicline producing a greater and longer-lasting reduction than cytisine. However, dose adjustment will have to be considered as a possible way to counter tolerance arising after continued use.

The expression of aquaporins 1 and 9 in adult rat epididymis is perturbed by chronic exposure to ethanol

Aquaporins (AQPs), notably AQP-1 and AQP-9, may contribute to reabsorption of fluid and solute across the epididymis. Ethanol is related to be a toxicant affecting directly or indirectly the epididymis and the sperm motility. This study examined the expression of AQP-1 and AQP-9 in adult epididymis of the UChA and UChB 10% (v/v) ethanol-preferring rats, focusing the ethanol-induced hormonal disturbances upon the regulation of these AQPs. Chronic ethanol intake significantly decreased body weight, while UChA and UChB rats displayed a marked loss of epididymal weights. Both ethanol-consuming animals had a severe reduction of testosterone levels, whereas LH and 17β-estradiol were unchanged. Throughout the epididymis, a strong reaction to AQP-1 was observed in myoid and endothelial cells of the UChB ethanol-preferring rats, differently from a moderate intensity in the initial segment of the UChA rats. In addition, AQP-9 showed a strong immunoreaction in the apical membrane of principal cells at initial segment. In cauda epididymis, the level of AQP-9 was reduced along the microvillus projections in both UChA and UChB rats compared to controls. We conclude that chronic ethanol consumption modulates the androgen levels, thereby modifying the expression pattern of AQP-1 and 9 in the epididymis.

Place conditioning with ethanol in rats bred for high (UChB) and low (UChA) voluntary alcohol drinking

The main goal of this study was to investigate the ability of an ethanol dose (1 g/kg) administered intraperitoneally to induce conditioned place preference (CPP) and/or conditioned place aversion (CPA) in two lines of rats selectively bred for their high (UChB) or low (UChA) voluntary ethanol intake. It was found that five pairings with ethanol induced CPA in ethanol-naïve rats of both lines, but the magnitude of avoidance was lower in the UChB relative to the UChA rats, indicating that ethanol was less aversive to naïve rats bred for high alcohol drinking. After 2 months of high voluntary ethanol drinking (∼6–7 g/kg/day), in free choice between 10% ethanol and water, ethanol produced CPP in UChB rats, reflecting that ethanol had become rewarding to these rats. By contrast, the low voluntary ethanol intake (<1 g/kg/day) displayed by UChA rats preexposed for 2 months in free choice did not change ethanol-induced CPA. However, preexposure of UChA rats to forced ethanol drinking (∼5.7 g/kg/day) and the later inhibition of ethanol-derived acetaldehyde by 4-methylpyrazole (10 mg/kg intraperitoneal), an inhibitor of the enzyme alcohol dehydrogenase, not only increased their voluntary ethanol intake in free choice, but also had a facilitating effect on the development of CPP. Taken together, these results show that the expression of the reinforcing effects of ethanol required a period of voluntary ethanol intake in UChB rats, whereas in UChA rats, both prior exposure to forced ethanol drinking and reduction of high blood ethanol-derived acetaldehyde were required.

Evaluation of the Uterine Tube Epithelium of UChA and UChB Rats (Ethanol Voluntary Consumers) During Estrus Phase.

Evaluation of the Uterine Tube Epithelium of UChA and UChB Rats (Ethanol Voluntary Consumers) During Estrus Phase.

Long-Term Exogenous Melatonin Regulates the Expression of Androgen, Estradiol and Progesterone Receptors in the Ovary, Oviduct and Uterus of Ethanol-Preferring Rats.

Chronic ethanol intake is associated with female hormonal dysfunction and it is well known that melatonin, an indolamine used for several therapies, plays key roles in regulating reproductive physiology. However its effects via sex steroid hormonal receptors remain inconclusive. Thus, this study was to evaluate how long-term melatonin exerts its regulatory effects on sex steroid receptors in ovary, oviduct and uterus of UChB rats chronically-exposed to ethanol (submitted to 10% (v/v) voluntary ethanol consumption). Forty adult female rats (n = 10/group) were finally selected for this study. UChB Co: drinking water only; UChB EtOH: drinking ethanol at 2-6 mL/100 g/day + water, both receiving 0.9% NaCl + 95% ethanol 0.04mL as vehicle. Concomitantly, UChB Co+M and UChB EtOH+M groups were infused with vehicle + melatonin [100 µg/100 g body weight/day] intraperitoneally for 60 days. All animals were euthanized by decapitation during the morning estrus (4 a.m.) and samples of ovaries, oviducts and uteri were collected and processed for western blot analysis of the melatonin receptor (MT1R), androgen receptor (AR), estrogen receptors (ER-α and ER-β) and progesterone receptors (PRA and PRB). Despite ovary AR has not been influenced by melatonin, both ethanol and ethanol + melatonin led to a decrease in oviduct AR levels, while only ethanol induced lower uterus AR compared to controls. Both ER-α and ER-β were underexpressed by either ethanol or melatonin in both ovary and oviduct and only ER-β showed low expression in uterus of the UChB EtOH and UChB Co+M rats. Conversely, PRA and PRB in the ovary were positively regulated by ethanol or ethanol + melatonin, whereas PRA was suppressed in uterus and oviduct, except when ethanol + melatonin were combined. Additionally, in melatonin-treated rats, regardless of ethanol consumption, there was an increase in ovary and uterus MT1R levels, in contrast to down-regulation of oviduct MT1R mediated by melatonin itself. We conclude that there are interactions between melatonin and ethanol on the expression pattern of androgen, estradiol and progesterone receptors in the ovary, oviduct and uterus of ethanol-preferring rats. Moreover, the responsiveness to androgen receptor is variable, enhancing or attenuating the ethanol effects in the ovary. Melatonin also potentiates the ethanol effects on oviduct and uterus. (poster)

Long-Term Exogenous Melatonin Treatment Modulates Overall Feed Efficiency and Protects Ovarian Tissue Against Injuries Caused by Ethanol-Induced Oxidative Stress in Adult UChB Rats

Chronic ethanol intake leads to reproductive damage including reactive oxygen species formation, which accelerates the oxidative process. Melatonin is known to regulate the reproductive cycle, food/liquid intake, and it may also act as a potent antioxidant indoleamine. The aim of this study was to verify the effects of alcoholism and melatonin treatment on overall feed efficiency and to analyze its protective role against the oxidative stress in the ovarian tissue of UChB rats (submitted to 10% [v/v] voluntary ethanol consumption). Forty adult female rats (n = 10/group) were finally selected for this study: UChB Co: drinking water only; and UChB EtOH: drinking ethanol at 2 to 6 ml/100 g/d + water, both receiving 0.9% NaCl + 95% ethanol 0.04 ml as vehicle. Concomitantly, UChB Co + M and UChB EtOH + M groups were infused with vehicle + melatonin (100 μg/100 g body weight/d) intraperitoneally over 60 days. All animals were euthanized by decapitation during the morning estrus (4 am). Body weight gain was reduced with ethanol plus melatonin after 40 days of treatment. In both melatonin-treated groups, it was observed a reduction in food-derived calories and liquid intake toward the end of treatment. The amount of consumed ethanol dropped during the treatment. Estrous cycle was longer in rats that received both ethanol and melatonin, with prolonged diestrus. Following to oxidative status, lipid hydroperoxide levels were higher in the ovaries of ethanol-preferring rats and decreased after melatonin treatment. Additionally, antioxidant activities of superoxide dismutase, glutathione peroxidase activity, and glutathione reductase activity were increased in melatonin-treated groups. We suggest that melatonin is able to affect feed efficiency and, conversely, it protects the ovaries against the oxidative stress arising from ethanol consumption.

IGFR-I expression and structural analysis of the hard palatine mucosa in an ethanol-drinking rat strain (UChA and UChB)

The study analyzed the effects of chronic alcohol ingestion on the ultrastructure of the lining epithelium of the hard palatine mucosa of rats UChA and UChB (lines with voluntary alcohol consumption) in order to contribute to the understanding of the consequences of alcohol abuse for the morphology of the digestive system. Thirty female adult animals aged 120 days were divided into three experimental groups. (1) Ten UChA rats (genetically low ethanol consumer) with voluntary intake of 10% v/v (5.45g/kg/day) ethanol solution and water. (2) Ten UChB (genetically high ethanol consumer) rats with voluntary intake of 10% v/v (7.16g/kg/day) ethanol solution and water. (3) Ten Wistar rats with voluntary ad libitum water intake (control group). Both groups received Nuvital pellets ad libitum. The IGFR-I expression was intense in both experimental groups. The epithelial cells of the alcoholic rats UChA and UChB showed many alterations such as the presence of lipid droplets, altered nuclei, nuclei in corneum layer and disrupted mitochondria. It was concluded that ethanol intake induces ultrastructural lesions in the hard palatine mucosa.

Mast Cells and Ethanol Consumption: Interactions in the Prostate, Epididymis and Testis of UChB Rats

Alcoholism has reached alarming proportions while fertility rates slowing in populations. The assessment of inflammatory effects with emphasis on the variation of the mast cells comparing ethanol chronic ingestion on reproductive organs deserves attention. The mast cells were investigated with light microscopy using toluidine blue to locate and count total mast cells and immunohistochemistry to identify the connective tissue mast cells (CTMC). The increase in total mast cells in the prostate, total and degranulated mast cells in epididymis of UChB rats was accompanied by a greater proportion of mucosal mast cells (MMC) in these organs. In addition, a lower incidence of degranulated mast cells was observed in epididymis of control rats. Ethanol increases the number of total and degranulated mast cells in the prostate and epididymis, as well as associated with increasing MMC, and therefore, it could be leading to inflammation in these organs.

Effect of Ethanol Deprivation and Re-Exposure on the Ethanol Drinking Behaviour of the High-Alcohol-Drinker (UChB) Rats

Alcohol addiction constitutes a major health problem in the general population, it is a complex pathology characterized by the development of tolerance, physical dependence and compulsive ethanol-seeking behaviour that often manifests as a chronic relapsing syndrome. 0ne of the major concerns in the treatment of alcohol-dependent patients is the prevention of relapse during periods of abstinence. The alcohol deprivation effect (ADE) is defined as a temporary increase in the voluntary intake of ethanol when it is reinstated after a period of alcohol deprivation and has been used as an animal model of relapse-like drinking. ADE can be used to evaluate the efficacy of possible pharmacological agents to prevent relapse drinking. The current study was undertaken to examine whether the high-alcohol-drinker UChB rats would display an ADE. Rats were given either continuous or periodic concurrent access to 10, 20% (vol/vol) of ethanol across deprivation cycles. UChB rats consuming ethanol voluntarily for two months, exhibit a robust ADE after a single deprivation period of two weeks. The increased alcohol intake during the early days of re-exposure, following a withdrawal phase, is attributed to a shift in preference towards the higher concentration of ethanol that might reflect an increase in craving for alcohol. Since an ADE is also observed in UChB rats, make this line of rats selectively bred for their high voluntary ethanol consumption, a useful model for study the efficacy of pharmacological agents for the treatment of relapse of alcohol consumption.

Alcoholism and coagulating gland: Androgen and insulin like growth factor-1 receptor features

The aim of this work was to characterize the structural and molecular changes in the coagulating gland from rats submitted to long-term alcohol treatment, as well as the possibility of recovery of these parameters after interrupting the alcohol administration. Ten Wistar and twenty UChB rats were divided into: Control group received tap water; Alcoholic group received 10% (v/v) ethanol daily for 150 days; and Abstinent group, received 10% (v/v) ethanol daily for 120 days and then tap water like the control for another 30 days. After 150 days, samples from the coagulating glands were processed for morphological and immunohistochemical analyses. The results showed atrophied epithelium and hypertrophied stroma, especially in the alcoholic group. Intensed androgen receptor (AR) immunolocalization was verified in the epithelium and weak in the stroma of the control group in relation to the other groups. Intensed insulin-like growth factor receptor-1 (IGFR-1) immunolocalization was verified in the stroma of the alcoholic and abstinent groups. Thus, it could be concluded that the excessive alcohol consumption caused morphological and molecular changes in the coagulating gland, characterizing the inverse relation of AR and IGFR-1 localization. The alcohol was an important factor in cellular mitosis occurrence, which could be fundamental element involved in glandular lesions.

Polymorphisms in mitochondrial genes encoding complex I subunits are maternal factors of voluntary alcohol consumption in the rat

Alcohol is detoxified in the liver by oxidizing enzymes that require nicotinamide adenine dinucleotide (NAD+) such that, in the rat, the availability of NAD+ contributes to control voluntary ethanol intake. The UChA and UChB lines of Wistar rats drink low and high amounts of ethanol respectively and differ in the capacity of their mitochondria to oxidize NADH into NAD+. This function resides in complex I of the respiratory chain and its variation is linked to genes transmitted through the maternal line. The aim of this study was to identify the genetic basis for the difference in the reoxidation of NADH in these nondrinker (UChA) and drinker (UChB) rats. Seven mitochondrial genes and two chromosome X genes encoding complex I subunits from rats of both lineages were amplified from liver DNA and sequenced. The UChA and UChB rat lines differ in their Nd2, Nd4, Nd5 and Nd6 mitochondrial genes and in the encoded proteins. Most noteworthy are ND2 and ND4 whose amino acid variations lead to changes in three-dimensional structure models. The ND2 proteins also differ in the number of predicted transmembrane domains. The Nd1 and Nd3 genes have silent substitutions, whereas Nd4L and the exonic sequences of the nuclear genes Ndufa1 and Ndufb11 show no differences between the UChA and UChB lines. Amino acid variations in four complex I subunits encoded in the mitochondrial genome may contribute to explain the differences between UChA and UChB rats in their capacity to reoxidize NADH and in their alcohol intake, suggesting that mitochondrial genes may constitute maternal factors of alcoholism.

PRECLINICAL STUDY: Effect of concurrent saccharin intake on ethanol consumption by high‐alcohol‐drinking (UChB) rats

This study examined the effect of concurrent presentation of a highly palatable saccharin solution on ethanol consumption during the acquisition or maintenance of ethanol drinking by high-alcohol-drinking (UChB) rats. Rats were exposed to ethanol (10% v/v) and water under a home cage, two-bottle, free-choice regimen with unlimited access for 24 hours/day. After 7 days (acquisition) of ethanol exposure, a third bottle containing saccharin (0.2% w/v) was concomitantly offered for an additional seven consecutive days, and the same process was repeated after 3 months (maintenance) of ethanol exposure. We found that concurrent saccharin intake significantly reduced ethanol intake by UChB rats after 7 days of ethanol exposure indicating that preference for sweet taste tends to override the preference for ethanol. However, the concurrent saccharin presentation to rats after 3 months of stable ethanol consumption did not reduce ethanol intake, whereas their saccharin consumption reached polydipsic-like values. These results support the notion that in UChB rats, a time-dependent sensitization to the rewarding effects of ethanol is developed that may account for the increases in ethanol volition seen following chronic ethanol intake.

Ovarian structure and hormonal status of the UChA and UChB adult rats in response to ethanol

Objectives In females, chronic alcoholism has a current and dangerous incidence to fertility. This work had the goal of elucidating the alterations on the ovary of UChA and UChB adult rats (ethanol 10% (v/v) voluntary drinkers). Study design After the treatment period, 42 female rats divided into three experimental groups (UChA, UChB and Wistar) suffered decapitation and their ovaries were removed and processed to further analysis on light and electron microscopy. The ovary was entirely sliced and stained by hematoxylin–eosin, toluidine blue, periodic acid Schiff (PAS) and Masson's tricromic. Thereby, the enzymatic reaction to acid and alkaline phosphatase, estral cyclicity, reproductive hormonal status and frequency in oestrous-related ovarian structures were assigned. Results The UChB rats showed an increase in body mass gain index and the ovaries relative weight was significantly lower comparing to the other groups. UCh rats presented the longest estral cycle durations and also persistent oestrous phasis, with uninterrupted cycles. Advanced follicular atresia was common in UCh animals, and degenerating intracellular fragments could be observed through acid phosphatase and electron microscopy techniques. Conclusions There were some estral cyclicity irregularities caused by chronic ethanol intake in the UCh groups which were consequently reflected as morphologic injury in the ovary structure.

Dopamine release in the nucleus accumbens (shell) of two lines of rats selectively bred to prefer or avoid ethanol

Lower tissue levels of dopamine and 5-hydroxytryptamine (5-HT) have been found in the nucleus accumbens of alcohol-naïve rats selectively bred to prefer ethanol than in rats bred to avoid it. These findings have led to the hypothesis that differences in the dopamine and 5-HT tone may be linked to ethanol preference. In the present study we used the in vivo microdialysis technique to determine the actual extracellular levels of dopamine, its metabolites 3,4-dihydroxyphenyl acetaldehyde (DOPALD), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-HT and 5-hydroxyindolacetic acid (5-HIAA) in the shell of nucleus accumbens of rat lines selectively bred as either high-ethanol (UChB) or low-ethanol (UChA) drinkers. Basal extracellular levels of dopamine, DOPALD, DOPAC and HVA were lower in the shell of nucleus accumbens of ethanol-naïve UChB than in UChA rats. In agreement, when perfused with 100 microM d-amphetamine or 100 mM KCl lower dopamine increases were observed in nucleus accumbens of UChB rats compared to UChA rats, indicating lower cytosolic (d-amphetamine releasable) and vesicular (KCl releasable) dopamine pools in UChB animals. Since the experiments were performed in ethanol-naïve rats, the present results suggest an innate deficiency in the mesolimbic dopamine system of UChB rats. There were no line differences in basal, d-amphetamine or KCl stimulated 5-HT levels. Thus, the present findings support a role of dopamine, but not of 5-HT, as predictor of ethanol preference in UChB rats. Overall, data obtained are in agreement with previous reports in other rat lines showing that lower dopamine levels and its metabolites are associated with a genetic predisposition to ethanol preference.

Morphologic changes in the urethral epithelium in an ethanol-drinking rat strain (UChA and UChB)

The extreme use of ethanol causes metabolic and pathologic changes in testes and urogenital system in different animal species. The enzyme alcohol dehydrogenase (ADH) catalyses the conversion of ethanol into carcinogenic metabolite acetaldehyde which is partly excreted into the urine. However, papers relating the chronic ethanol consumption to the urethral morphology are unknown. This work evaluates the toxic effect of the chronic ethanol ingestion on the urethral epithelium of UChA and UChB rats. Conventional techniques of histology, histochemistry, immunohistochemistry and ultrastructural analysis were used. The analysis showed the presence of lipid drops and intercellular spaces in the epithelial cells in the urethra of UChA and UChB rats compared to control rats. Urethral neuroendocrine cell were observed and characterized for presenting vesicles containing electron-dense granules associated with nervous fibers. We conclude that the chronic consumption of ethanol induces the presence lipid drops in the epithelial cells of the urethra of UChA and UChB rats. The NE cells of the urethra of UChA and UChB rats did not show alterations under chronic effect of the ethanol.