The University of Southampton
University of Southampton Institutional Repository

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

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.

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.

Full text not available from this repository.

More information

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


Local EPrints ID: 56591
ISSN: 0014-2999
PURE UUID: d4a21ead-a8c5-4986-8e1d-5624189d19fb
ORCID for John E. Chad: ORCID iD

Catalogue record

Date deposited: 07 Aug 2008
Last modified: 12 Oct 2017 01:39

Export record


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

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton:

ePrints Soton supports OAI 2.0 with a base URL of

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.