Baclofen blocks postsynaptic inhibition but not the effect of muscimol in the olfactory cortex

Abstract

1The olfactory cortex slice preparation from the guinea-pig brain was used to study the effects of baclofen on inhibition using intracellular recording. Stimulation of the lateral olfactory tract activates sequentially excitatory and inhibitory pathways. Inhibition is manifest as a period of increased membrane conductance (termed postsynaptic inhibitory conductance, IPSC).2 Bath application of baclofen (0.2-50011M) reversibly blocked the IPSC. Baclofen also produced a secondary increase in the amplitude and duration of the initial excitatory postsynaptic potential.3 Baclofen (0.5-500 tM) slightly augmented the ability of bath-applied muscimol to increase the resting membrane conductance. Baclofen had no effect on cell excitability and membrane potential and no effect on the action of 'y-aminobutyric acid (GABA), noradrenaline, glycine, taurine or 5-hydroxytrypamine. 4 These results confirm previous suggestions that baclofen at low concentrations acts outside the GABA receptor mediating the IPSC perhaps by reducing the release of the excitatory transmitter activating the inhibitory interneurones.

Dual population of GABAA and GABAB receptors in rat pars intermedia demonstrated by release of αMSH caused by barium ions

“…Consequently less Ca2+ would penetrate the cells, so reducing the efficiency of the excitationsecretion coupling. Our finding that the basal release declines by about 25% in the presence of (-)-baclofen argues in favour of such an interpretation: minimum changes of firing rate and alterations of Ca2+-dependent action potentials being observed in other preparations (see Dunlap, 1981;Scholfield, 1983). In principle, when tested against the Ba2+ stimulus, one would predict an equivalent decrease in hormone output (also reflecting the average firing rate).…”

Involvement of GABA systems in feedback regulation of glutamate‐and GABA‐mediated synaptic potentials in rat neostriatum.

“…(-)-Baclofen may also produce postsynaptic effects caused either by an increase of potassium conductances (Newberry & Nicoll, 1984;Gaihwiler & Brown, 1985;Lacey, Mercuri & North, 1988) or by an inhibition of calcium currents (Dunlap, 1981;Dolphin & Scott, 1987). Finally, (-)-baclofen depresses Cl--mediated, bicuculline-sensitive inhibitory postsynaptic potentials in various central neurones (Scholfield, 1983;Misgeld, Klee & Zeise, 1986).…”

The Neuropharmacology of Baclofen

“…That baclofen reduces stimulation-evoked GABAergic inhibition in the olfactory cortex and the hippocampus was suggested from extracellular recordings of field potentials [6,24]. Intracellular studies in vitro have shown that baclofen reduces the amplitude of short-latency GABAA receptor-mediated IPSPs evoked in various hippocampal neurons [14, 60,73], neurons in the olfactory cortex [96], and neurons in the frontal neocortex [55,56,102]. These depressions of IPSP amplitudes are not due to the concomitant action of baclofen to hyperpolarize these neurons.…”

“…Short-latency IPSPs in rat neocortical neurons are also GABAA receptor-mediated [100,101], and baclofen's depressions of these IPSPs were independent of membrane potential between values of -50 and -110 mV [56]. Importantly, baclofen's reductions of short-latency GABAergic IPSPs in olfactory cortical and neocortical neurons were shown to be accompanied by reductions in the conductance increases measured during these IPSPs [56,96]. Because baclofen does not reduce responses to exogenously applied GABA or muscimol in these same neurons (see below), a postsynaptic blockade of the IPSP conductance can be excluded and these results argue strongly that baclofen reduces GABAA receptor-mediated IPSPs by a presynaptic action.…”

“…Baclofen applications that reduce the conductance increases associated with stimulation-evoked GABAergic IPSPs have no effect on conductance increases produced by the direct application of GABA or the GABAA agonist muscimol [56,96]. Even at high concentrations, baclofen had no effect on currents evoked in neocortical neurons by iontophoretically applied GABA [56].…”