Purpose: We evaluated the possible additive effect induced by the administration of the anticonvulsant vigabatrin (VGB) and cholecystokinin-8 sulfate (CCK-8S) on an experimental model of partial complex seizures (maximal dentate gyrus activation, MDA). Moreover, the functional involvement of γ-aminobutyric acid (GABA) neurotransmission was tested by iontophoretically administering bicuculline (GABA receptor antagonist) in the dentate gyrus. Methods: Urethane anesthetized rats were pretreated with VGB (50, 100 or 200 mg/kg, i.p.) or CCK-8S (8 nmol/kg, i.p.) alone or coadministered with VGB (50 mg/kg, i.p.). Dentate gyrus epileptic activity was obtained through the repetitive electrical stimulation of the angular bundle. MDA latency, duration, and poststimulus afterdischarge (AD) duration were evaluated. The extracellular activity of some dentate neurons was recorded before and during bicuculline iontophoresis. Results: Only the higher dose of VGB reduced the mean duration of dentate MDA and AD. CCK-8S significantly decreased the number of animals exhibiting MDA responses, characterized by increased latency and shorter duration. The coadministration of CCK-8S and VGB (50 mg/kg) significantly increased the anticonvulsant effects, either reducing the number of responding animals or decreasing both MDA and AD durations. During bicuculline iontophoresis, all the modifications induced on the MDA-related activity of dentate neurons by the pretreatments (VGB and/or CCK-8S) were abolished. Discussion: The results indicate that CCK-8S significantly enhances the VGB-induced anticonvulsant effect in the MDA model of partial epilepsy, probably through an increase of GABA cerebral levels. Such increased anticonvulsant effect becomes evident by using VGB at a lower dose.

Ferraro, G., Sardo, P. (2009). Cholecystokinin-8 sulfate modulates the anticonvulsant efficacy of vigabatrin in an experimental model of partial complex epilepsy in the rat. EPILEPSIA, 50(4), 721-730 [10.1111/j.1528-1167.2008.01956.x].

Cholecystokinin-8 sulfate modulates the anticonvulsant efficacy of vigabatrin in an experimental model of partial complex epilepsy in the rat

FERRARO, Giuseppe;SARDO, Pierangelo
2009-01-01

Abstract

Purpose: We evaluated the possible additive effect induced by the administration of the anticonvulsant vigabatrin (VGB) and cholecystokinin-8 sulfate (CCK-8S) on an experimental model of partial complex seizures (maximal dentate gyrus activation, MDA). Moreover, the functional involvement of γ-aminobutyric acid (GABA) neurotransmission was tested by iontophoretically administering bicuculline (GABA receptor antagonist) in the dentate gyrus. Methods: Urethane anesthetized rats were pretreated with VGB (50, 100 or 200 mg/kg, i.p.) or CCK-8S (8 nmol/kg, i.p.) alone or coadministered with VGB (50 mg/kg, i.p.). Dentate gyrus epileptic activity was obtained through the repetitive electrical stimulation of the angular bundle. MDA latency, duration, and poststimulus afterdischarge (AD) duration were evaluated. The extracellular activity of some dentate neurons was recorded before and during bicuculline iontophoresis. Results: Only the higher dose of VGB reduced the mean duration of dentate MDA and AD. CCK-8S significantly decreased the number of animals exhibiting MDA responses, characterized by increased latency and shorter duration. The coadministration of CCK-8S and VGB (50 mg/kg) significantly increased the anticonvulsant effects, either reducing the number of responding animals or decreasing both MDA and AD durations. During bicuculline iontophoresis, all the modifications induced on the MDA-related activity of dentate neurons by the pretreatments (VGB and/or CCK-8S) were abolished. Discussion: The results indicate that CCK-8S significantly enhances the VGB-induced anticonvulsant effect in the MDA model of partial epilepsy, probably through an increase of GABA cerebral levels. Such increased anticonvulsant effect becomes evident by using VGB at a lower dose.
2009
Ferraro, G., Sardo, P. (2009). Cholecystokinin-8 sulfate modulates the anticonvulsant efficacy of vigabatrin in an experimental model of partial complex epilepsy in the rat. EPILEPSIA, 50(4), 721-730 [10.1111/j.1528-1167.2008.01956.x].
File in questo prodotto:
File Dimensione Formato  
Ferraro and Sardo, 2009, Epilepsia.pdf

Solo gestori archvio

Descrizione: Articolo principale
Dimensione 729.08 kB
Formato Adobe PDF
729.08 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10447/35244
Citazioni
  • ???jsp.display-item.citation.pmc??? 3
  • Scopus 14
  • ???jsp.display-item.citation.isi??? 13
social impact