ELSEVIER Neuroscience Letters 216 (1996) 121-124 NEURUSCIENC[ [EIT[ilS Gamma-hydroxybutyric acid decreases thalamic sensory excitatory postsynaptic potentials by an action on presynaptic GABAB receptors Zsuzsa Emri, K~oly Antal, Vincenzo Crunelli* Physiology Unit, School of Molecular and Medical Biosciences, University of Wales Cardiff, Museum Avenue, Cardiff, CF1 1SS, UK Received 12 June 1996; revised version received 20 August 1996; accepted 22 August 1996 Abstract The effect of gamma-hydroxybutyric acid (GHB) on the excitatory postsynaptic potential (EPSP) evoked in thalamocortical neurones of the rat dorsal lateral geniculate nucleus and ventrobasal thalamus was investigated in vitro, GHB (0.1-5 mM) dose-dependently and reversibly decreased (36-78%) the amplitude of the sensory EPSP. This effect of GHB was blocked by the GABABreceptor antagonist CGP 35348 (1 mM). NCS 382 (1-3 mM), a putative GHB receptor antagonist, did not antagonise but weakly potentiated both the GHB- and baclofen-mediated decrease of the EPSP amplitude. Keywords: Gamma-hydroxybutyric acid; GABAB receptor; Excitatory postsynaptic potential; Dorsal lateral geniculate nucleus; Ven- trobasal thalamus; Absence epilepsy Gamma-hydroxybutyric acid (GHB) is a naturally occurring substance synthetised primarily from GABA and present at relatively high concentration in the thala- mus [12]. Specific high-affinity binding sites, uptake sys- tems and metabolising enzymes for GHB have been identified [1,3,6], and it has therefore been suggested that GHB might function as a neurotransmitter or neuro- modulator [11,12]. Binding studies have shown a weak affinity of GHB for GABAB receptors in cortex and thala- mus when using baclofen and the agonist CGP 27492 as ligands [4], but no effect of GHB when using GABA as a ligand for GABAB receptors [10]. In addition, the putative GHB receptor antagonist NCS 382 has proved useful in separating the effect of GHB on GABAB receptors from that on GHB receptors [8]. An action for endogenous GHB has not been demon- strated, but systemic administration of GHB to experimen- tal animals produces a variety of dose-dependent effects, including changes in behavioural state [ 11] and generation of behavioural and EEG activities that resemble human absence epilepsy [9,10]. Indeed, systemic injection of GHB is an established pharmacological model for this type of epilepsy [10]. Microdialysis experiments in the * Correspondingauthor. Tel.: +44 1222874801; fax: +44 1222874986; e-mail: crunelli@ cardiff.ac.uk ventrobasal thalamus (VB) in vivo have shown a GHB- mediated decrease in the extracellular concentration of both GABA and glutamate, an effect that appears to involve presynaptic GHB receptors since it was partially blocked by the putative GHB receptor antagonist NCS 382 [2]. A previous study in the dorsal lateral geniculate nucleus (dLGN) in vitro, however, has shown that the action of GHB on thalamocortical (TC) neurones, includ- ing the generation of rhythmic burst firing via the intrinsic pacemaker ('delta') oscillation [7], was abolished by CGP 35348 and not by NCS 382, suggesting an involvement of postsynaptic GABAB but not of GHB receptors [ 131. Since presynaptic GABAB receptors are also present in the dLGN and VB where they inhibit excitatory amino acid release [5], this study was undertaken to investigate the effect of GHB on thalamic sensory EPSP in the dLGN and VB, and to ascertain whether GHB acts on presynaptic GABAB or GHB receptors. The preparation and maintenance of rat dLGN and VB slices, that did not contain the nucleus reticularis thalami were similar to those described previously [5,13]. Briefly, male Wistar rats (150-200 g) were decapitated and a block of tissue containing the dLGN or the VB (ventral poster- olateral and ventral posteromedial nuclei) was separated from the rest of the brain. Slices (400 #m) were maintained in an interface-type slice bath and perfused with warmed 0304-3940/96/$12.00 © 1996Elsevier Science Ireland Ltd. All rights reserved Pll S0304-3940(96) 13016-0