Blockade of GABA(B) receptors facilitates muscarinic agonist-induced epileptiform activity in immature rat piriform cortex in vitro.

Libri, V., Constanti, A., Postlethwaite, M. and Bowery, N.G. (1998) Blockade of GABA(B) receptors facilitates muscarinic agonist-induced epileptiform activity in immature rat piriform cortex in vitro. Naunyn-Schmiedeberg's Archives of Pharmacology, 358 (2). pp. 168-174. 10.1007/PL00005239.

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DOI: 10.1007/PL00005239

Abstract

The effects of the selective GABA(B) receptor antagonist [3-[[(3,4-dichlorophenyl)methyl]aminolpropyl] (diethoxymethyl) phosphinic acid (CGP 52432) on muscarinic (mAChR) and metabotropic glutamate (mGluR) responsiveness were studied in slices of piriform cortex from both immature (P16-P22) and adult (> or =P40) rats, using a conventional intracellular recording technique. In both adult and immature slices, CGP 52432 (1 microM) had no effect on neuronal membrane properties, whereas it selectively abolished the late inhibitory postsynaptic potential (IPSP) evoked by local electrical stimulation of association fibre terminals. Age-related changes in mAChR (but not mGluR) responsiveness were also detected. In adult neurones, bath-application of the mAChR agonist oxotremorine-M (OXO-M; 10 microM), or the selective mGluR agonist 1S,3R-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD; 10 microM) evoked similar membrane depolarization and inhibition of evoked excitatory postsynaptic potentials (EPSPs). However, while 1S,3R-ACPD and OXO-M produced indistinguishable slow excitatory effects in immature slices, during superfusion with OXO-M, neurones exhibited spontaneous paroxysmal depolarizing shifts (PDSs) that were suppressed in the presence of atropine (1 microM) or the selective GABA(B) receptor agonist beta-parachlorophenyl-gamma-aminobutyric acid [(-)baclofen; 10 microM]. Also, application of OXO-M resulted in a pronounced prolongation (rather than a decrease) of electrically evoked postsynaptic potentials (PSPs) which now exhibited recurrent superimposed spike discharges. In adult slices, in the continuous presence of CGP 52432 (1 microM; 20 min pre-incubation), a subsequent exposure to 10 microM OXO-M or 1S,3R-ACPD failed to induce any spontaneous epileptiform activity, and evoked PSPs were consistently suppressed. In contrast, in immature slices, after incubation in CGP 52432 (1 microM; 20 min), a subsequent application of a low dose of OXO-M (2.5 microM), which was inactive per se, was able to produce spontaneous PDSs and a prolongation of evoked PSPs. We conclude that a reduction in GABA(B)-mediated synaptic inhibition in immature slices (in co-operation with other factors) may contribute to the facilitation of excitatory neurotransmission and therefore play a role in the generation of mAChR-induced epileptiform activity.

Item Type:Article
Uncontrolled Keywords:Muscarinic agonist-induced epileptiform - activity - GABAB receptors - CGP 52432 - Piriform - cortex - Synaptic transmission - Intracellular recording
Departments, units and centres:Department of Pharmacology > Department of Pharmacology
ID Code:2518
Journal or Publication Title:Naunyn-Schmiedeberg's Archives of Pharmacology
Deposited By:Library Staff
Deposited On:25 Nov 2011 08:54
Last Modified:25 Nov 2011 08:57

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