Electrophysiological actions of GABA(B) agonists and antagonists in rat dorso-lateral septal neurones in vitro

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 mu M tetrodotoxin to prevent indirect neuronal effects caused by action potential-dependent neurotransmitter release, bath application of baclofen (0.1-30 mu M) or SK&F 97541 (0.01-3 mu M) evoked concentration-dependent hyperpolarizations which reversed close to the potassium equilibrium potential; the EC(50)s were 0.55 and 0.05 mu M, respectively. No significant desensitization was observed during prolonged agonist exposure (less than or equal to 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 mu M) 91+/-5%, CGP 52432 (1 mu M) 64+/-5%, CGP 35348 (100 mu M) 82+/-5%, CGP 36742 (100 mu M) 76+/-8%, and 2-OH saclofen (100 mu 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.