Cocaine withdrawal enhances pentobarbital-induced sleep in rats: evidence of GABAergic modulation.
We intended to clarify whether pentobarbital-induced sleep in rats is affected during cocaine withdrawal and whether GABAergic systems are involved in this sleep. Cocaine (20mg/kg) was administered subcutaneously (s.c.) to rats once per day for 6 days. Pentobarbital (42mg/kg) was administered intraperitoneally (i.p.) to the rats 1 day (acute withdrawal), 8 days (subacute withdrawal), or 14 days (subchronic withdrawal) after withdrawal from cocaine. All rats were fasted for 24h prior to the pentobarbital injection. Pentobarbital-induced sleeping time was significantly increased during both acute and subacute withdrawal, while sleeping onset latency was not affected. However, sleeping time recovered to normal 14 days after withdrawal. Protein levels of GABAA receptor gamma-subunits and glutamic acid decarboxylase (GAD) were increased in both acute and subacute cocaine withdrawal in the hypothalamus, but were normal after 14 days of withdrawal. These results indicate that pentobarbital-induced sleeping time in cocaine withdrawal is transiently increased. Hypersomnia in cocaine withdrawal might be influenced by functional changes in the GABAergic systems.
Ma
Yuan
Y
Research Institute of Veterinary Medicine, Chungbuk National University, Cheongju 361-763, South Korea.
Ma
Hong
H
Hong
Jin-Tae
JT
Kim
Yun-Bae
YB
Nam
Sang-Yoon
SY
Oh
Ki-Wan
KW
D000779:Anesthetics, Local / Q000008:administration & dosage*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000378:metabolism / Q000503:physiopathology*; D004357:Drug Synergism; D018757:GABA Modulators / Q000494:pharmacology*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D008297:Male; D010424:Pentobarbital / Q000494:pharmacology*; D021122:Protein Subunits / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism; D012890:Sleep / Q000187:drug effects*; D013375:Substance Withdrawal Syndrome; D013997:Time Factors
D000779:Anesthetics, Local; D018757:GABA Modulators; D021122:Protein Subunits; D011963:Receptors, GABA-A; D005968:Glutamate Decarboxylase; D010424:Pentobarbital; D003042:Cocaine