Unilateral microinjection of carbenoxolone into the pontis caudalis nucleus inhibits the pentylenetetrazole-induced epileptiform activity in rats

Neurosci Lett. 2015 Aug 18:602:38-43. doi: 10.1016/j.neulet.2015.06.037. Epub 2015 Jun 30.

Abstract

Pontine reticular formation (PRF) is involved in the generation and maintenance of generalized epileptic seizures. Carbenoxolone (CBX) is a gap junction blocker with anticonvulsant properties. Therefore, the present study was designed to explore the effects of CBX microinjected into the pontis caudalis nucleus (PnC) on generalized tonic-clonic seizures (GTCS) and epileptiform activity induced by pentylenetetrazole (PTZ). All control rats presented GTCS after a single dose of PTZ. The microinjection of CBX into the PnC reduced the GTCS incidence induced by PTZ. Moreover, the CBX significantly increased the latency to the first myoclonic jerk. Additionally, CBX significantly decreased the spectral power and the amplitude of the epileptiform activity induced by PTZ. By contrast, the microinjection of a gap junction opener (trimethylamine) did not cause anticonvulsant effects and even increased the duration of the GTCS. These findings suggest that the PnC is a particular nucleus where the CBX could exert its action mechanisms and elicit anticonvulsant effects.

Keywords: Carbenoxolone; Gap junctions; Pentylenetetrazole; Pontine reticular formation; Seizures.

MeSH terms

  • Animals
  • Anticonvulsants / pharmacology*
  • Anticonvulsants / therapeutic use
  • Carbenoxolone / pharmacology*
  • Carbenoxolone / therapeutic use
  • Epilepsy / chemically induced
  • Epilepsy / physiopathology*
  • Male
  • Microinjections
  • Pentylenetetrazole*
  • Pontine Tegmentum / drug effects*
  • Pontine Tegmentum / physiopathology
  • Rats, Wistar
  • Seizures / physiopathology

Substances

  • Anticonvulsants
  • Carbenoxolone
  • Pentylenetetrazole