Nicotinic effects on excitatory field potentials recorded from the immature CA3 area of rat hippocampal slices.
We investigated the nicotinic modulation of the excitatory field potentials recorded from the immature (postnatal day 10-20) hippocampal CA3 area, in the presence of the GABA(A) antagonist bicuculline methiodide (BMI, 10 microM). Nicotine (50 microM) enhanced the evoked field potentials; its effects were also observed in the presence of the GABA(B) antagonist 2-hydroxy-saclofen (250 microM; added to BMI) and were blocked by pre-perfusion with the nicotinic antagonist hexamethonium (HXM, 50 microM). The potentiating effects of nicotine in BMI persisted during prolonged perfusion (more than 20 min), while those in control perfusion medium were transient. The nicotinic antagonists HXM (50 microM), methyllycaconitine (MLA, 0.01 microM) and dihydro-beta-erythroidine (DHbetaE, 50 microM) potentiated CA3-evoked field potentials. Perfusion of HXM in the presence of the anticholinesterase eserine (1 microM) or the muscarinic antagonist atropine (1 microM) did not alter its effects. None of the nicotinic agents tested changed the frequency of spontaneous BMI-induced epileptiform discharges (nicotine, HXM, MLA, DhbetaE), suggesting that nicotinic receptors do not drive spontaneous epileptiform discharges in this in vitro model. These experiments demonstrate that nicotinic receptors are activated tonically during disinhibition and modulate the activity of excitatory synapses in the immature CA3 hippocampal area. The persistent nicotinic facilitatory effects during disinhibition versus the transient in control conditions indicate that nicotinic modulation depends on environmental conditions and also that nicotinic receptors may be a contributing factor in early-life seizures.
Psarropoulou
Caterina
C
Ste-Justine Hospital Research Center, Department of Pediatrics, Université de Montréal, 3175 Côte-Ste-Catherine, H3T 1C5, Montreal, QC, Canada, caterina.psarropoulou@umontreal.ca
Boivin
Melissa
M
Laudadio
Mark Anthony
MA
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000031:analogs & derivatives* / Q000494:pharmacology; D018738:Hexamethonium / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology*; D066298:In Vitro Techniques; D009538:Nicotine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018738:Hexamethonium; C017069:bicuculline methiodide; D009538:Nicotine; D001640:Bicuculline