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2-Hydroxy-saclofen causes a phaclofen-reversible reduction in population spike amplitude in the rat hippocampal slice

Record type: Article

2-Hydroxy-saclofen is known to be active at GABAB receptors in the mammalian central nervous system, and we have investigated its effects on synaptic transmission in the rat hippocampal slice preparation. Orthodromic stimuli were applied to the stratum radiatum, and population spike responses from the CA1 pyramidal cell layer were recorded extracellularly. A second, identical stimulus was applied at a variable interpulse interval (IPI) after the initial conditioning stimulus. GABAergic synaptic inhibition was observed as a decrease in the spike amplitude of the second response compared to the first. Both the GABAB receptor antagonist phaclofen (1 mM) and 2-hydroxy-saclofen (200 ?M) prevented a slow phase of inhibition for IPIs of 200–400 ms. However, these agents differed markedly in their effects on overall synaptic transmission. Phaclofen had no effect on the amplitude of the initial conditioning spike amplitude, whereas 2-hydroxy-saclofen reduced it significantly, in a manner similar to baclofen (1 ?M). The direct actions of 2-hydroxy-saclofen were unexpected for a pure antagonist of GABAB receptors, but could be prevented by the co-administration of phaclofen (1 mM), but not bicuculline (1 ?M). Reduction in conditioning spike amplitude due to antagonism of GABAB autoreceptors on inhibitory interneurones and subsequent enhancement of GABAA tonic inhibition would have been blocked by bicuculline. The blockade of the 2-hydroxy-saclofen effect by phaclofen implies a GABAB receptor partial agonist action. The possible sites of this action are discussed.

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Citation

Caddick, Sarah J., Stanford, Ian M. and Chad, John E. (1995) 2-Hydroxy-saclofen causes a phaclofen-reversible reduction in population spike amplitude in the rat hippocampal slice European Journal of Pharmacology, 274, pp. 41-46. (doi:10.1016/0014-2999(94)00702-9).

More information

Published date: 14 February 1995
Keywords: GABA (?-aminobutyric acid), GABAB receptor, 2-hydroxy-saclofen, hippocampus, (Inhibition), Presynaptic inhibition

Identifiers

Local EPrints ID: 56591
URI: http://eprints.soton.ac.uk/id/eprint/56591
ISSN: 0014-2999
PURE UUID: d4a21ead-a8c5-4986-8e1d-5624189d19fb
ORCID for John E. Chad: ORCID iD orcid.org/0000-0001-6442-4281

Catalogue record

Date deposited: 07 Aug 2008
Last modified: 17 Jul 2017 14:30

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Contributors

Author: Sarah J. Caddick
Author: Ian M. Stanford
Author: John E. Chad ORCID iD

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