Long-term reduction of benzodiazepine receptor density in the rat cerebellum by acute seizures and kindling and its recovery 6 months later by a pentylenetetrazole challenge.
Seizures induced by an acute pentylenetetrazole (50 mg/kg) injection were accompanied by a long-term (at 1-48 h, but not on day 7) decrease in the density (B(max)) of [3H]-diazepam binding to benzodiazepine receptors in rat cerebellar cortex with no change in affinity (K(d)). Kindling for 24 days by daily administrations of pentylenetetrazole (20 mg/kg) led to the same decrease in benzodiazepine receptor density (at 1-48 h, but not on day 7) as that observed after a single dose of pentylenetetrazole (50 mg/kg). This suggests a common mechanism for both acute and kindling-induced seizures, dependent on the long-term receptor changes. The increased susceptibility to seizures persisted for 6 months after the termination of kindling, with BDZ receptor density in cerebellar cortex reduced almost by half. In age-matched controls, an acute dose of PTZ (30 mg/kg) induced seizures and decrease in both B(max) and K(d) of [3H]-diazepam binding. In kindled rats, at 6 months post-kindling, the same dose of PTZ (30 mg/kg) restored the benzodiazepine receptor density to the level found 6 months before, at the time of termination of kindling. Also, the severity of seizures was enhanced in the kindled rats. The results are discussed in terms of a balance of inhibitory and excitatory processes, in which the reduced BDZ receptor density at 6 months post-kindling may represent a compensatory reaction to outbalance some alterations in excitatory systems that have been reported to be induced by kindling.
Bazyan
A S
AS
Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Butlerov St. 5A, GSP-7, 117865, Moscow, Russia. bazyan@mail.ru
Zhulin
V V
VV
Karpova
M N
MN
Klishina
N Y
NY
Glebov
R N
RN
D000208:Acute Disease; D000375:Aging / Q000378:metabolism; D000818:Animals; D002531:Cerebellum / Q000378:metabolism*; D003292:Convulsants; D003975:Diazepam / Q000493:pharmacokinetics; D004334:Drug Administration Schedule; D004827:Epilepsy / Q000139:chemically induced / Q000378:metabolism*; D018756:GABA Antagonists; D007696:Kindling, Neurologic / Q000378:metabolism*; D008297:Male; D010433:Pentylenetetrazole / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*; D013995:Time
D003292:Convulsants; D018756:GABA Antagonists; D011963:Receptors, GABA-A; D003975:Diazepam; D010433:Pentylenetetrazole