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 (20 mg/kg) was administered subcutaneously (s.c.) to rats once per day for 6 days. Pentobarbital (42 mg/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 24 h 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 γ-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.