title: Antiabsence effects of carbenoxolone in two genetic animal models of absence epilepsy (WAG/Rij rats and lh/lh mice).
abstract: 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.
authors.affiliation: Section of Pharmacology, Department of Experimental and Clinical Medicine, Faculty of Medicine and Surgery, University of Catanzaro, Via T. Campanella 115, 88100 Catanzaro, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Gareri
authors.forename: Daniele
authors.initials: D
authors.lastname: Condorelli
authors.forename: Natale
authors.initials: N
authors.lastname: Belluardo
authors.forename: Rita
authors.initials: R
authors.lastname: Citraro
authors.forename: Vincenza
authors.initials: V
authors.lastname: Barresi
authors.forename: Angela
authors.initials: A
authors.lastname: Trovato-Salinaro
authors.forename: Angela
authors.initials: A
authors.lastname: Trovato-Salinato
authors.forename: Giuseppa
authors.initials: G
authors.lastname: Mudò
authors.forename: Guido Ferreri
authors.initials: GF
authors.lastname: Ibbadu
authors.forename: Emilio
authors.initials: E
authors.lastname: Russo
authors.forename: Giovambattista
authors.initials: G
authors.lastname: De Sarro
mesh_terms: 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
chemical_list: D017630:Connexins; D002229:Carbenoxolone