Effects of Dexmedetomidine on Rat Locus Coeruleus and Ethanol Withdrawal Symptoms During Intermittent Ethanol Exposure

Abstract

In the present study, the neuroprotective effects of dexmedetomidine on rat locus coeruleus were studied during a 5-week intermittent ethanol exposure. Male Wistar rats (3 to 4 months old) were given ethanol or isocaloric sucrose by intragastric intubations three times a day for 4 days, which was followed by a 3-day withdrawal period. This 7-day cycle of ethanol exposure and withdrawal was repeated five times. Dexmedetomidine (at a dose decreasing from 30 microg/kg to 10 microg/kg, s.c.) was given to the treatment group during the withdrawal phase. The results showed that, during the 5-week experiment, dexmedetomidine significantly relieved the ethanol withdrawal syndrome, measured as the sum of the three most specific symptoms (rigidity, tremor, and irritability). The total neuron number of locus coeruleus (LC) decreased in the ethanol-treated group by 24%, compared with the nontreated control group and by 11%, compared with the sucrose-treated control group. Interestingly, the LC neuron numbers were found to decrease in the sucrose-intubated rats as well, compared with the nontreated control group. Dexmedetomidine was found to relieve ethanol-induced neuronal loss in the LC. Dexmedetomidine might be a new interesting alternative in the treatment of ethanol withdrawal syndrome, particularly due to its possible neuroprotective effects in the central nervous system.