Characteristic changes of the GABAA receptor in the brain of phenobarbital-dependent and withdrawn rats.
The changes of the GABAA receptor in the brain of phenobarbital (PB)-dependent and -withdrawn rats were investigated using [3H]-muscimol (a potent agonist of GABAA receptor) as the ligand. The dissociation constant for a low affinity binding site (Kd2) of PB-dependent rats significantly increased without affecting the high affinity site (Kd1) and Bmax for both sites. A decrease of specific [3H]-muscimol binding was observed in the whole brain and the cerebellum of the PB-dependent rats, when examined at a fixed drug concentration of 2 nM. Moreover, the specific [3H]-muscimol binding in the withdrawn rats was remarkably lower than that of the dependent rats. These results suggest that the change of the GABAA receptor may be related to the development of PB-dependence and -withdrawal.
Tanaka
S
S
Department of Biochemical Toxicology, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
Aoki
K
K
Satoh
T
T
Yoshida
T
T
Kuroiwa
Y
Y
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000648:ultrastructure*; D008297:Male; D008566:Membranes / Q000378:metabolism; D009118:Muscimol / Q000378:metabolism / Q000493:pharmacokinetics; D010634:Phenobarbital / Q000009:adverse effects*; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*; D019966:Substance-Related Disorders / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism / Q000648:ultrastructure; D014018:Tissue Distribution; D014316:Tritium
D011963:Receptors, GABA-A; D014316:Tritium; D009118:Muscimol; D010634:Phenobarbital