EFFECTS OF MUSCIMOL OR HOMOTAURINE ON SLEEP-WAKE STATES IN ALCOHOL-DEPENDENT RATS DURING WITHDRAWAL

Sleep-wake states were studied following withdrawal in 36 adult male w istar alcohol-dependent rats, after chronic administration of ethanol (10 g/kg/24 h) for 13 days. In the light phase of the withdrawal day, 12 alcohol-dependent rats received muscimol (0.25 mg/kg), 12 received homotaurine (140 mg/kg), and 12 received 0.9% physiological saline (10 ml/kg). The results have been compared with a control group of 36 rat s that received water during the treatement phase of the experiment, a nd the 14th day received intraperitoneal muscimol or homotaurine. Musc imol significantly improves the alterations of sleep-wake states in al cohol-withdrawn rats, decreasing the percentage of active wakefulness and increasing the percentage of REMS, but without any action on the l atency of appearance of REMS, which remains shortened. The effects of homotaurine are less important on the wakefulness, but it also increas es the percentage of REMS without influencing its latency of appearanc e. The influence of these GABA(A) agonists is not identical during the whole period of survey in the light phase, as there are important dif ferences in the temporal sequences for each of them. We conclude that the stimulation of GABA(A) receptors, of which the activity is decreas ed during alcohol withdrawal, significantly improves the disturbances in the sleep-wake states in the alcohol-dependent rats, in a time-rela ted manner, and there are significant pharmacodynamic differences betw een muscimol and homotaurine. (C) 1998 Elsevier Science Inc.