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Electrophysiological actions of GABA B agonists and antagonists in rat dorso‐lateral septal neurones in vitro
Author(s) -
Bon Christelle,
Galvan Martin
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb15493.x
Subject(s) - gabab receptor , baclofen , postsynaptic potential , agonist , inhibitory postsynaptic potential , chemistry , pharmacology , gabaa receptor , electrophysiology , neurotransmitter , receptor , biology , medicine , endocrinology , neuroscience , biochemistry
1 The actions of GABA B ‐receptor agonists and antagonists on rat dorso‐lateral septal neurones in vitro were recorded with intracellular microelectrodes. 2 In the presence of 1 μ m tetrodotoxin to prevent indirect neuronal effects caused by action potential‐dependent neurotransmitter release, bath application of baclofen (0.1–30 μ m ) or SK&F 97541 (0.01–3 μ m ) evoked concentration‐dependent hyperpolarizations which reversed close to the potassium equilibrium potential; the EC 50 s were 0.55 and 0.05 μ m , respectively. No significant desensitization was observed during prolonged agonist exposure (≤ 10 min). 3 Hyperpolarizations induced by baclofen were antagonized in a competitive manner by the following GABA B ‐receptors antagonists (calculated pA 2 values in parentheses): CGP 36742 (4.0), 2‐OH saclofen (4.2), CGP 35348 (4.5), CGP 52432 (6.7) and CGP 55845A (8.3). Responses to SK&F 97541 were also antagonized by CGP 55845A (pA 2 = 8.4). 4 The amplitude of the late, GABA B receptor‐mediated inhibitory postsynaptic potential (i.p.s.p.) was reduced by the GABA B antagonists as follows (means ± s.e.mean): CGP 55845A (1 μ m ) 91 ± 5%, CGP 52432 (1 μ m ) 64 ± 5%, CGP 35348 (100 μ m ) 82 ± 5%, CGP 36742 (100 μ m ) 76 ± 8%, and 2‐OH saclofen (100 μ m ) 68 ± 3%. 5 It is concluded that neurones in the rat dorso‐lateral septal nucleus express conventional GABA B receptors, which are involved in the generation of slow inhibitory postsynaptic potentials. CGP 55845A is the most potent GABA B receptor antagonist described in this brain area.