[Suppressive effect of GABA-containing liposomes on kindled convulsion].
gamma-aminobutyric acid (GABA), a major neurotransmitter in the mammalian brain, may be natural mediator of defence against epileptic activities. When given peripherally, however, GABA itself can cross the blood-brain barrier (BBB) insufficiently. Liposomes (LIPO), being composed of lipid bilayers in which various compounds can be entrapped, have been shown to cross the BBB. Recently, Loeb et al. demonstrated that intraperitoneal injection of GABA entrapped within LIPO (GABA-L) significantly suppresses penicillin- or isoniazid-induced seizures in rats. In the present study, we examined the effect of intraperitoneally administered GABA-L on the kindled amygdala (AM) seizures in addition to the comparative uptake of radioactivity by brain following intraperitoneal administration of 3H-GABA-L or 3H-GABA in rats. Expt. I: Anticonvulsant effect of GABA-L Twelve male Wistar rats weighing 250-300 g were used. Bipolar electrodes made of twisted stainless steel wire 0.2 mm in diameter were implanted into the left AM. All the animals were kindled at the left AM until a stable kindled seizure was evoked for at least five successive days. Subsequently, the stimulus intensity was gradually reduced and the last intensity to induce the kindled seizure was designated as the generalized seizure triggerring threshold (GST). GABA was dissolved in deionized water at a concentration of 0.5 g/ml. GABA-L and LIPO were prepared as follows. 80 mumoles L-alpha-phosphatidylcholine, 22.8 mumoles stearylamine and 11.4 mumoles cholesterol were dissolved in chloroform. After chloroform was removed under a stream of nitrogen gas, dried thin film of phospholipids was formed.(ABSTRACT TRUNCATED AT 250 WORDS)
Mori
N
N
Department of Neuropsychiatry, Fukushima Medical College, Japan.
Terayama
K
K
Sato
T
T
Kumashiro
H
H
D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism / Q000473:pathology; D003864:Depression, Chemical; D004337:Drug Carriers; D007274:Injections, Intraperitoneal; D007696:Kindling, Neurologic / Q000187:drug effects*; D008081:Liposomes; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D014316:Tritium; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use
D000927:Anticonvulsants; D004337:Drug Carriers; D008081:Liposomes; D014316:Tritium; D005680:gamma-Aminobutyric Acid