ISSN:
1432-1912
Keywords:
Key words: GABA-B – Hippocampus GABA – Receptors – GABA-B antagonists
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract. The synaptic release of γ-aminobutyric acid (GABA) is thought to be regulated by presynaptic GABA receptors of the B-type. It was the goal of this study to validate this concept electrophysiologically using four selective antagonists of GABA-B receptors. Experiments were performed in hippocampal slices exposed to 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX 30 μM) and D-2-amino-5-phosphonopentanoate (AP5 40 μM) in order to block excitatory transmission. Consequently, electrical stimulation of the Schaffer collateral/commissural fibers evoked monosynaptic inhibitory potentials (IPSP) recorded intracellularly from CA1 pyramidal neurons. In a test called paired-pulse paradigm two identical stimuli were applied at intervals ranging from 350 to 4000 ms. The IPSP evoked by the second stimulation was smaller in its amplitude over the entire interval range. This reduction of the second GABA-response is thought to result from the activation of presynaptic GABA receptors. The GABA-uptake inhibitor SKF 89976 (100 μM) increased the amplitude of the IPSP‘s and increased the ratio of the first to the second IPSP amplitude. These findings indicate that the drug increases the GABA content in the synaptic cleft leading to a facilitation of paired-pulse depression. The actions of four bath-applied GABA-B receptor antagonists were examined in the paired-pulse paradigm. None of these compounds abolished paired-pulse inhibition completely even at concentrations higher than those required to block postsynaptic GABA-B responses. The potent GABA-B antagonists CGP 55845 and CGP 52432 reduced paired-pulse depression by 80% at 10 μM (maximal effect). The other two compounds, CGP 46381 and CGP 36742 had no significant or only a subtle effect respectively. The adenosine receptor antagonist, caffeine (100 μM) and the metabotropic excitatory amino acid receptor antagonist (1S, 3R)-1-aminocyclopentane-1,3-dicarboxylic acid (MCPG, 1 mM)) had no effect on paired-pulse depression in the presence of CGP 55845 (10 μM). In conclusion since all CGP compounds are GABA-B antagonists at postsynaptic sites these findings suggest that there may be differences between the pre- and postsynaptic GABA-B receptors. Apart from presynaptic GABA-B receptors there appear to exist additional mechanisms involved in paired-pulse depression that remain to be elucidated.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00169135
Permalink
