Exaggeration of epileptic-like patterns by nicotine receptor activation during the GABA withdrawal syndrome

Carmen Silva-Barrat, Julio Velluti, Magdolna Szente, Cesira Batini, Jean Champagnat

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

To understand how nicotinic cholinergic receptors may participate in epileptic seizures, we tested the effects of nicotine and of the competitive nicotinic antagonists dihydro-β-erythroidine and α-bungarotoxin on synaptic paroxysmal depolarization shifts (PDSs) and intrinsic bursts of action potentials recorded in slices from rats presenting a cortical status epilepticus. This model named GABA-withdrawal syndrome (GWS) appears consecutive to the interruption of a prolonged intracortical GABA infusion. Effects of both nicotinic antagonists suggest a distinct involvement of α4-β2 and α7 subunits in shaping individual PDSs and patterning repetitive bursts. On one hand, in GWS rats, an increase of PDS latency and prolongation of PDS and bursts were induced by nicotine and reduced by dihydro-β-erythroidine, but not by α-bungarotoxin. The K+ blocker tetraethylammonium also increased duration without changing latency. Thus, dihydro-β-erythroidine- sensitive receptors exert distinct controls on the presynaptic generation of PDS and on the process which terminates PDSs and bursts. On the other hand, α-bungarotoxin depolarized neurons and generated rhythmic discharges of clustered bursts. Clustered bursts were also observed in slices obtained from GWS rats treated with the acetylcholinesterase inhibitor eserine. We suggest that both dihydro-β-erythroidine and α-bungarotoxin-sensitive sites control paroxysmic activities in GWS and could be involved in some human and animal epilepsies presenting mutations of nicotinic cholinergic receptors.

Original languageEnglish
Pages (from-to)133-143
Number of pages11
JournalBrain research
Volume1042
Issue number2
DOIs
Publication statusPublished - May 3 2005

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Keywords

  • Nicotinic modulation
  • Rat epileptogenic focus

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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