Long-term and regional specific changes in [3H]flunitrazepam binding in kindled rat hippocampus.

Abstract:

:The binding of the GABAA/benzodiazepine receptor agonist [3H]flunitrazepam was studied in the hippocampus of rats kindled by daily stimulation of the Schaffer collaterals, using semi-quantitative autoradiography. Two kindled stages were investigated: (i) 24 h after the last generalized tonic-clonic seizure (fully kindled) and (ii) 28 days after the last generalized seizure (long-term). The binding of [3H]flunitrazepam was determined at two concentrations, 3 and 16 nM. In the CA1 area, we found a small but significant decrease (ca. 10%), both in the 3 and 16 nM [3H]flunitrazepam binding at the fully kindled stage. In contrast, there was a significant increase in the 3 nM binding (c. 15%) at the long-term stage. The 16 nM binding was not significantly different from control binding at this stage. In the granular and molecular layers of the fascia dentata, we found at both kindled stages a significantly increased 3 nM (ca. 9 and 19%, respectively) and 16 nM (ca. 19 and 14%, respectively) binding. Furthermore, we found that muscimol was still able to enhance the [3H]flunitrazepam binding in kindled animals, indicating that the GABAA receptor agonist binding site and benzodiazepine agonist binding site are still functionally coupled. The changes in [3H]flunitrazepam binding at the fully kindled stage are in agreement with the recently observed kindling-induced changes in [3H]muscimol binding in the hippocampal formation of the same animals [Titulaer M. N. G. et al. (1994) Neuroscience 59, 817-826] and extend these observations to the benzodiazepine modulatory site of the GABAA receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

journal_name

Neuroscience

journal_title

Neuroscience

authors

Titulaer MN,Kamphuis W,Lopes da Silva FH

doi

10.1016/0306-4522(95)00158-f

subject

Has Abstract

pub_date

1995-09-01 00:00:00

pages

399-406

issue

2

eissn

0306-4522

issn

1873-7544

pii

030645229500158F

journal_volume

68

pub_type

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