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 wistar 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 rats that received water during the treatment phase of the experiment, and the 14th day received intraperitoneal muscimol or homotaurine. Muscimol significantly improves the alterations of sleep-wake states in alcohol-withdrawn rats, decreasing the percentage of active wakefulness and increasing the percentage of REMS, but without any action on the latency of appearance of REMS, which remains shortened. The effects of homotaurine are less important on the wakefulness, but it also increases the percentage of REMS without influencing its latency of appearance. The influence of these GABA(A) agonists is not identical during the whole period of survey in the light phase, as there are important differences in the temporal sequences for each of them. We conclude that the stimulation of GABA(A) receptors, of which the activity is decreased during alcohol withdrawal, significantly improves the disturbances in the sleep-wake states in the alcohol-dependent rats, in a time-related manner, and there are significant pharmacodynamic differences between muscimol and homotaurine.
Rouhani
S
S
Service de Physiologie-Explorations fonctionnelles, Hopital Cochin, Paris, France.
Dall'Ava-Santucci
J
J
Bajenaru
O
O
Emmanouilidis
E
E
Tran
G
G
Manicom
R
R
Dinh-Xuan
A T
AT
Poenaru
S
S
D000435:Alcoholic Intoxication / Q000523:psychology; D000437:Alcoholism / Q000523:psychology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000097:blood; D000431:Ethanol / Q000097:blood; D018755:GABA Agonists / Q000494:pharmacology*; D008297:Male; D009118:Muscimol / Q000494:pharmacology*; D017286:Polysomnography / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012890:Sleep / Q000187:drug effects*; D013375:Substance Withdrawal Syndrome / Q000523:psychology*; D013654:Taurine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014851:Wakefulness / Q000187:drug effects*
D002492:Central Nervous System Depressants; D018755:GABA Agonists; D013654:Taurine; D009118:Muscimol; D000431:Ethanol; C001355:tramiprosate