Bidirectional effects of beta-carbolines in rats with spontaneous petit mal-like seizures.

Abstract:

:Seven benzodiazepine-receptor ligands of the beta-carbolines' group were administered IP in Wistar rats from (1) a strain displaying spontaneous petit mal-like seizures (PMLS) characterized by spike and wave discharges (SWD) and, (2) a strain where no seizure is ever observed (NS). Five different types of effects were observed. (1) Injection of a full agonist (ZK 93 423) suppressed SWD in PMLS rats, in a dose-dependent manner, and induced marked sedation with alteration of EEG background activity; (2) Injection of partial agonists (ZK 95 962, ZK 91 296) suppressed SWD in PMLS rats without sedation; (3) Injection of low doses of a full inverse agonist (DMCM) significantly increased the total duration of SWD in PMLS rats and induced SWD in NS rats. Higher doses of DMCM induced convulsions in both strains; (4) Injection of partial inverse agonists (FG 7142, ZK 90 886) aggravated SWD in PMLS and induced SWD in NS rats. FG 7142 induced convulsions only in PMLS animals, whereas no convulsions were ever observed with ZK 90 886; (5) Injection of an antagonist (ZK 93 426) did not significantly modify SWD in PMLS rats. However, this compound was able to reverse both antiepileptic effects of agonists and epileptogenic effects of inverse agonists. These results suggest the involvement of the benzodiazepine-GABA receptor complex in the control of petit mal-like seizures in rats.

journal_name

Brain Res Bull

journal_title

Brain research bulletin

authors

Marescaux C,Vergnes M,Jensen LH,Petersen E,Depaulis A,Micheletti G,Warter JM

doi

10.1016/0361-9230(87)90101-8

subject

Has Abstract

pub_date

1987-09-01 00:00:00

pages

327-35

issue

3

eissn

0361-9230

issn

1873-2747

pii

0361-9230(87)90101-8

journal_volume

19

pub_type

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