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 [H-3]-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 [H-3]-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 precesses, 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. (C) 2001 Elsevier Science B.V. All rights reserved.