Antiabsence effects of carbenoxolone in two genetic animal models of absence epilepsy (WAG/Rij rats and lh/lh mice).
Carbenoxolone (CBX), the succinyl ester of glycyrrhetinic acid, is an inhibitor of gap junctional intercellular communication. We have tested its possible effects upon two genetic animal models of epilepsy (WAG/Rij rats and lethargic (lh/lh) mice). Systemic administration of CBX was unable to significantly affect the occurrence of absence seizures in WAG/Rij rats. In particular, intravenous (5-40 mg/kg) or intraperitoneal (i.p.; 10-80 mg/kg) administration of CBX was unable to significantly modify the number and duration of spike-wave discharges (SWDs) in WAG/Rij rats, whereas the bilateral microinjection (0.05, 0.1, 0.5 and 1 microg/0.5 microl) of CBX into nucleus reticularis thalami (NRT) and nucleus ventralis posterolateralis (VPL) thalami produced a decrease in the duration and the number of SWDs. Bilateral microinjection of CBX into nucleus ventroposteromedial (VPM) thalami did not produce any significant decrease in the number and duration of SWDs. On the contrary, i.p. (5-40 mg/kg) or intracerebroventricular (0.5, 1, 2 and 4 microg/2 microl) administration of CBX in lh/lh mice induced a marked decrease in the number and duration of SWDs in a dose-dependent manner. At the doses used no movement disorders, or other behavioural changes, were recorded in both WAG/Rij rats and lh/lh mice. No effects were observed in both animal models following systemic or focal administration of glycyrrhizin into the same brain areas where CBX was shown to be effective.
Gareri
Pietro
P
Section of Pharmacology, Department of Experimental and Clinical Medicine, Faculty of Medicine and Surgery, University of Catanzaro, Via T. Campanella 115, 88100 Catanzaro, Italy.
Condorelli
Daniele
D
Belluardo
Natale
N
Citraro
Rita
R
Barresi
Vincenza
V
Trovato-Salinaro
Angela
A
Trovato-Salinato
Angela
A
Mudò
Giuseppa
G
Ibbadu
Guido Ferreri
GF
Russo
Emilio
E
De Sarro
Giovambattista
G
D000818:Animals; D001345:Autoradiography / Q000379:methods; D002229:Carbenoxolone / Q000627:therapeutic use*; D017630:Connexins / Q000145:classification / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects; D004832:Epilepsy, Absence / Q000188:drug therapy* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D051379:Mice; D008818:Mice, Neurologic Mutants; D051381:Rats; D011919:Rats, Inbred Strains; D013787:Thalamic Nuclei / Q000187:drug effects; D013997:Time Factors
D017630:Connexins; D002229:Carbenoxolone