Field and intracellular recordings were made in an in vitro slice preparation to establish whether the antiepileptic drugs topiramate andlamotrigine modulate cholinergic excitation in the rat subiculum. Bath application of carbachol (CCh, 70e100 mM) induced: (i) spontaneousand synchronous field oscillations (duration ¼ up to 7 s) that were mirrored by intracellular depolarizations with rhythmic action potentialbursts; and (ii) depolarizing plateau potentials (DPPs, duration ¼ up to 2.5 s) associated with action potential discharge in response to brief(50e100 ms) intracellular depolarizing current pulses. Ionotropic glutamatergic receptor antagonists abolished the field oscillations withoutinfluencing DPPs, while atropine (1 mM) markedly reduced both types of activity. Topiramate (10e100 mM, n ¼ 8e13 slices) or lamotrigine(50e400 mM, n ¼ 3e12) decreased in a dose-dependent manner, and eventually abolished, CCh-induced field oscillations. During topiramateapplication, these effects were accompanied by marked DPP reduction. When these antiepileptic drugs were tested on DPPs recorded in thepresence of CCh þ ionotropic glutamatergic and GABA receptor antagonists, only topiramate reduced DPPs (n ¼ 5e19/dose; IC50 ¼ 18 mM,n ¼ 48). Similar effects were induced by topiramate during metabotropic glutamate receptor antagonism (n ¼ 5), which did not influenceDPPs. Thus, topiramate and lamotrigine reduce CCh-induced epileptiform synchronization in the rat subiculum but only topiramate is effectivein controlling DPPs. We propose that muscarinic receptor-mediated excitation represents a target for the action of some antiepileptic drugs suchas topiramate.

Antiepileptic drugs and muscarinic receptor-dependent excitation in the rat subiculum / M., D'Antuono; H., Kawasaki; C., Palmieri; Curia, Giulia; Biagini, Giuseppe; M., Avoli. - In: NEUROPHARMACOLOGY. - ISSN 0028-3908. - STAMPA. - 52:5(2007), pp. 1291-1302. [10.1016/j.neuropharm.2007.01.008]

Antiepileptic drugs and muscarinic receptor-dependent excitation in the rat subiculum.

CURIA, GIULIA;BIAGINI, Giuseppe;
2007

Abstract

Field and intracellular recordings were made in an in vitro slice preparation to establish whether the antiepileptic drugs topiramate andlamotrigine modulate cholinergic excitation in the rat subiculum. Bath application of carbachol (CCh, 70e100 mM) induced: (i) spontaneousand synchronous field oscillations (duration ¼ up to 7 s) that were mirrored by intracellular depolarizations with rhythmic action potentialbursts; and (ii) depolarizing plateau potentials (DPPs, duration ¼ up to 2.5 s) associated with action potential discharge in response to brief(50e100 ms) intracellular depolarizing current pulses. Ionotropic glutamatergic receptor antagonists abolished the field oscillations withoutinfluencing DPPs, while atropine (1 mM) markedly reduced both types of activity. Topiramate (10e100 mM, n ¼ 8e13 slices) or lamotrigine(50e400 mM, n ¼ 3e12) decreased in a dose-dependent manner, and eventually abolished, CCh-induced field oscillations. During topiramateapplication, these effects were accompanied by marked DPP reduction. When these antiepileptic drugs were tested on DPPs recorded in thepresence of CCh þ ionotropic glutamatergic and GABA receptor antagonists, only topiramate reduced DPPs (n ¼ 5e19/dose; IC50 ¼ 18 mM,n ¼ 48). Similar effects were induced by topiramate during metabotropic glutamate receptor antagonism (n ¼ 5), which did not influenceDPPs. Thus, topiramate and lamotrigine reduce CCh-induced epileptiform synchronization in the rat subiculum but only topiramate is effectivein controlling DPPs. We propose that muscarinic receptor-mediated excitation represents a target for the action of some antiepileptic drugs suchas topiramate.
52
5
1291
1302
Antiepileptic drugs and muscarinic receptor-dependent excitation in the rat subiculum / M., D'Antuono; H., Kawasaki; C., Palmieri; Curia, Giulia; Biagini, Giuseppe; M., Avoli. - In: NEUROPHARMACOLOGY. - ISSN 0028-3908. - STAMPA. - 52:5(2007), pp. 1291-1302. [10.1016/j.neuropharm.2007.01.008]
M., D'Antuono; H., Kawasaki; C., Palmieri; Curia, Giulia; Biagini, Giuseppe; M., Avoli
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11380/448172
Citazioni
  • ???jsp.display-item.citation.pmc??? 6
  • Scopus 13
  • ???jsp.display-item.citation.isi??? 12
social impact