Effects of Ageing and Intermittent Ethanol Exposure on Rat Locus Coeruleus and Ethanol-Withdrawal Symptoms

Abstract

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.

Effects of Lifelong Ethanol Consumption on Brain Monoamine Transmitters in Alcohol-Preferring Alko Alcohol (AA) Rats

“…Intermittent ethanol exposure (5.8 g/kg/day four days a week for 5.5 months) was previously found to induce significant loss of noradrenergic neurons in rat superior cervical ganglion, while no neuron loss occurred in rats exposed to similar amounts of ethanol continuously [36]. Moreover, loss of locus coeruleus noradrenergic neurons was seen in aged rats (29–30 months old) after only 5 weeks of intermittent exposure to heavily intoxicating doses of ethanol [37]. On the other hand, formation of acetaldehyde adducts, possible mediators of ethanol-induced toxicity, was reported in the frontal cortex and cerebellum of AA and ANA rats given a continuous ethanol treatment similar to the present one [20].…”

Age‐associated changes in mRNA levels of Phox2, norepinephrine transporter and dopamine β‐hydroxylase in the locus coeruleus and adrenal glands of rats

“…However, more recent cell counting studies show no age-related neuronal loss in the human LC up to 80 years of age (Mouton et al 1994;Kubis et al 2000). Furthermore, no age-related loss of LC neurons has been reported in Fischer 344 rats up to 32 months of age (Goldman and Coleman 1981), in Wistar rats up to 30 months of age (Riihioja et al 1999), and in AA (Alko, Alcohol) rats up to 24 months of age (Lu et al 1997;Rintala et al 1998). Hence, current data regarding age-related loss of LC neurons is somewhat controversial.…”

“…2000). Furthermore, no age‐related loss of LC neurons has been reported in Fischer 344 rats up to 32 months of age (Goldman and Coleman 1981), in Wistar rats up to 30 months of age (Riihioja et al . 1999), and in AA (Alko, Alcohol) rats up to 24 months of age (Lu et al .…”

Differences in Behavioral Responding in Adult and Aged Rats Following Chronic Ethanol Exposure

“…During each 24-hour EtOH-free period, observational withdrawal signs were assessed at 2, 4, 8, 12, and 24 hours post-EtOH using a standardized behavioral rating scale assessing rigidity, tremor, irritability, and hypoactivity, as described previously (Hemmingsen et al, 1984;Riihioja et al, 1999). The total score was defined as the sum of each of the scores from the 4 categories as agreed upon by 2 experimenters.…”