[Changes in GABAA/benzodiazepine receptor complex function in the pentobarbital-dependent rat].
Changes in GABAA receptor function were studied in pentobarbital (PB)-dependent rats. Physical dependence on PB in male Lewis rats was induced by the drug-admixed food method. The 36Cl- influx into cerebral cortical synaptoneurosomes induced by 10 microM GABA in the PB-dependent rat was significantly decreased compared with the control. The enhancement of GABA-dependent 36Cl- influx by the addition of PB, ethanol (EtOH) and flunitrazepam (FZ) was not recognized in the PB-dependent group. The addition of picrotoxin and bicuculline had no effect on GABA-dependent 36Cl- influx in PB-dependent rats. In the [3H]muscimol binding assay of low affinity sites of the GABAA receptor, Kd was significantly increased and Bmax was significantly decreased in PB-dependent rats compared with the control. However, these values were similar between PB-dependent and control rats in the study of [3H]FZ binding to benzodiazepine (BZ) receptors. The present study indicates that GABAergic transmission involving GABA-dependent chloride channels was altered in PB dependent rats. This alteration of the GABAA/BZ/chloride channel complex function may be related to the cross-tolerance among barbiturates, BZ and EtOH.
Nabeshima
A
A
Department of Neuropsychiatry, School of Medicine, Sapporo Medical University, Japan.
Saito
T
T
Takahata
N
N
D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D015536:Down-Regulation; D004361:Drug Tolerance; D066298:In Vitro Techniques; D008297:Male; D010424:Pentobarbital; D051381:Rats; D011917:Rats, Inbred Lew; D018079:Receptors, GABA / Q000378:metabolism / Q000502:physiology*; D011963:Receptors, GABA-A / Q000378:metabolism / Q000502:physiology*; D019966:Substance-Related Disorders / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D018079:Receptors, GABA; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D010424:Pentobarbital