Acute desensitization of presynaptic GABAB-mediated inhibition and induction of epileptiform discharges in the neonatal rat hippocampus

The European Journal of Neuroscience
Patrizia TosettiO Caillard

Abstract

The consequences of sustained activation of GABA(B) receptors on GABA(B)-mediated inhibition and network activity were investigated in the neonatal rat hippocampus using whole-cell and extracellular field recordings. GABA(B)-mediated presynaptic control of gamma-aminobutyric acid (GABA) release progressively diminished with time in spite of the continued presence of the agonist (100 microM baclofen, 15 min), indicating acute desensitization of presynaptic GABA(B)-mediated inhibition on GABAergic terminals. By contrast, neither GABA(B)-mediated inhibition of glutamate release nor postsynaptic GABA(B)-mediated inhibition seemed to produce this desensitization. Efficacy of presynaptic GABA(B) receptors was still reduced by 49% 30 min after baclofen washout, suggesting a long timeframe for recovery from desensitization. The 15-min baclofen application was followed by a dramatic modification of the spontaneous network activity, with the occurrence of epileptiform events called ictal-like discharges (ILDs). Extracellular field recordings confirmed the epileptic nature of the discharges that could be recorded up to 4 h after baclofen washout. ILDs did not occur when the GABA(B) receptor antagonist CGP35348 was coapplied with baclofen....Continue Reading

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Citations

Jul 28, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Reagan L PennockShane T Hentges
Jul 2, 2011·Pharmacology & Therapeutics·Jean-Luc GaiarsaChristophe Porcher
May 26, 2006·The EMBO Journal·Stéphanie M PontierMichel Bouvier
Sep 21, 2011·European Journal of Pharmacology·Ahmad A Khundakar, Tyra S C Zetterström
Sep 2, 2009·Epilepsy & Behavior : E&B·Gregory L Holmes
Sep 29, 2004·Biochemical Pharmacology·Seb J ThuaultAndrew R Calver
Apr 23, 2005·Anesthesia and Analgesia·Sethuraman ManikandanRamesh C Rathod

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