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The alcohol-preferring AA (Alko Alcohol) rats are more rapidly sensitized to the locomotor activity-stimulating effects of small doses of morphine than the alcohol-avoiding ANA (Alko Non-Alcohol) rats. To study the involvement of dopaminergic and serotonergic transmission in this behaviour, the effects of acute morphine (1 mg/kg) challenge on the concentrations of dopamine (DA), 5-hydroxytryptamine (5-HT, serotonin) and their metabolites were estimated in three dopaminergic areas in AA and ANA rats on the fourth day after a 3-day morphine or saline treatment. Acute administration of morphine enhanced DA metabolism in the caudate-putamen in the AA, but not in the ANA, rats; in the nucleus accumbens and in the olfactory tubercle the acute effect of morphine was similar in rats of both lines. Morphine pretreatment did not significantly enhance acute morphine's effects on DA metabolites in any of the brain areas studied in rats of either line. Acute administration of morphine enhanced brain 5-HT metabolism in the AA rats but not in the ANA rats, but after repeated treatment it induced no enhancement of 5-HT metabolism. With the methods used, no significant differences were found between the AA and ANA rats in the effects of repeated morphine on cerebral dopaminergic or serotonergic mechanisms which could account for the different behavioural sensitization found previously in rats of these lines. However, both monoamines studied might be involved in the acute locomotor stimulatory effects of morphine. [ABSTRACT FROM PUBLISHER]

Acetaldehyde, the first metabolite of ethanol, has been shown to be capable of binding covalently to liver proteins in vivo, which may be responsible for a variety of toxic effects of ethanol. Acetaldehyde–protein adducts have previously been detected in the liver of patients and experimental animals with alcoholic liver disease. Although a role for acetaldehyde as a possible mediator of ethanol-induced neurotoxicity has also been previously suggested, the formation of protein–acetaldehyde adducts in brain has not been examined. This study was designed to examine the occurrence of acetaldehyde–protein adducts in rat brain after lifelong ethanol exposure. A total of 27 male rats from the alcohol-preferring (AA) and alcohol-avoiding (ANA) lines were used. Four ANA rats and five AA rats were fed 10–12% (v/v) ethanol for 21 months. Both young (n = 10) and old (n = 8) rats receiving water were used as controls. Samples from frontal cortex, cerebellum and liver were processed for immunohistochemical detection of acetaldehyde adducts. In four (two ANA, two AA rats) of the nine ethanol-exposed rats, weak or moderate positive reactions for acetaldehyde adducts could be detected both in the frontal cortex and cerebellum, whereas no such immunostaining was found in the remaining five ethanol-treated rats or in the control rats. The positive reaction was localized to the white matter and some large neurons in layers 4 and 5 of the frontal cortex, and to the molecular layer of the cerebellum. Interestingly, the strongest positive reactions were found among the ANA rats, which are known to display high acetaldehyde levels during ethanol oxidation. We suggest that acetaldehyde may be involved in ethanol-induced neurotoxicity in vivo through formation of adducts with brain proteins and macromolecules. [ABSTRACT FROM PUBLISHER]

In this study, the effects of ethanol and age on the morphology of the locus coeruleus (LC) and on the severity of ethanol-withdrawal symptoms were studied during a 5-week intermittent ethanol exposure. Young (3–4 months) and old (29–30 months) male Wistar rats were given highly intoxicating doses of ethanol by intragastric intubations for 4 days, followed by a 3-day ethanol-withdrawal period. This 7-day cycle of ethanol exposure and withdrawal was repeated five times. A non-treated group and a sucrose-fed group of both ages were used as control groups. The severity of ethanol-withdrawal symptoms (rigidity, tremor, irritability, hypoactivity) was rated up to 62 h after the last dose of ethanol. The intoxication level was higher in the old, compared with the young, rats, despite the smaller doses of ethanol given to the old animals. There was no significant difference between the age groups in the severity of the ethanol-withdrawal syndrome. The LC quantitative studies were performed using unbiased stereological methods. The results showed that there was no difference between the age groups in the LC total neuron numbers of the non-treated control groups. The 5-week intermittent ethanol exposure significantly reduced the LC neuron numbers and LC neuronal density in the old ethanol-exposed animals, compared with the sucrose-fed control animals. In the young rats, the ethanol-induced neuron loss did not reach statistical significance. According to the ANCOVA, the difference in the ethanol-induced LC neuronal loss between the age groups may be due to the difference in the intoxication levels. Interestingly, the sucrose intubations were also found to decrease the LC neuronal numbers in the young rats, compared with the non-treated young control group. It was concluded that ageing did not significantly affect the severity of ethanol-withdrawal symptoms or ethanol-induced loss of LC neurons in Wistar rats. [ABSTRACT FROM PUBLISHER]

The effects of lifelong ethanol consumption and ageing on the morphology of locus coeruleus (LC) were studied in alcohol-preferring AA (Alko Alcohol) rats of both sexes. Ethanol (12% v/v) was the only available liquid for the ethanol-consuming rats from 3 months up to 24 months of age. Young (3-month-old) and old (24-month-old) control groups were included in the measurements. The LC morphometry was performed by an unbiased disector method. In the old control rats, the total neuron number, neuronal density and the volume of the LC proper did not differ from the young controls. In the ethanol-exposed rats, the total neuron number of the LC was decreased by 30% and the LC neuronal density by 22%, compared to the age-matched controls. No gender difference was found in the vulnerability of LC neurons to ethanol-induced degeneration. The results suggest a remarkable sensitivity of the LC neurons to the ethanol-induced degeneration in both male and female rats. The possible mechanisms and functional implications of this neuronal loss are discussed. [ABSTRACT FROM PUBLISHER]