THE ACTIONS OF BACLOFEN ON NEURONS AND SYNAPTIC TRANSMISSION IN THE NUCLEUS-TRACTUS-SOLITARII OF THE RAT INVITRO

1. Intracellular and whole-cell patch recordings were made from sixty-seven neurones located in the nucleus tractus solitarii (NTS) in transverse slices of rat brainstem, 2. Baclofen at concentrations of 2-20 mum caused hyperpolarization from normal resting membrane potentials (V(m)). This response was associated with a decrease in input resistance (R(m)) tested by current pulses in discontinuous current clamp mode when membrane potential was restored to control level by current injection. In single electrode discontinuous voltage clamp mode, baclofen at these concentrations caused a small (< 50 pA) outward current associated with increased membrane conductance measured by voltage steps from holding potentials (V(h)) of - 50 or - 60 mV. Current-voltage relations at these V(h)s and the results of varying V(h) between - 50 and - 110 mV during responses to baclofen gave a reversal potential of - 73 mV. The amplitudes of baclofen responses were related to K+ concentration tested by comparing responses in media containing 1-24 mm extracellular K+, indicating that postsynaptically baclofen acts via a K+ conductance. 3. These effects were still apparent in the presence of tetrodotoxin (which did not abolish all spontaneous synaptic activity) and also in medium containing a combination of Co2+, the excitatory amino acid antagonist 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX) and the GABA(A) antagonist bicuculline which blocked synaptic activity. 4. The amplitude and frequency of spontaneous postsynaptic potentials (spPSPs) and spontaneous postsynaptic currents (spPSCs) were reduced by baclofen at concentrations (1 muM or less) which had no effect on membrane potential or holding current in current or voltage clamp recordings respectively. 5. The amplitude of evoked excitatory (evEPSPs/evEPSCs) and inhibitory (evIPSPs/evIPSCs) synaptic events elicited by electrical stimulation in the vicinity of the tractus solitarius (TS) was reduced by low concentrations of baclofen (250 nm-1 muM) which did not produce discernible postsynaptic responses. 6. In order to examine the effects of baclofen on excitatory synaptic events without contamination with inhibitory events, stimulation of the TS was carried out in the presence of bicuculline. Conversely to investigate actions on purely inhibitory synaptic responses experiments were carried out with CNQX in the bathing solution. Inhibitory synaptic responses could still be evoked, presumably by stimulation of interneurones in the vicinity of the TS. IPSPs/IPSCs were more sensitive to baclofen than EPSPs/EPSCs. 7. The effects of baclofen on membrane potential or holding current and PSP/PSCs were antagonized by 2-hydroxysaclofen (400 muM) confirming that baclofen was acting at gamma-aminobutyric acid (GABA)B receptors. 8. The pre- and postsynaptic depressant effects of baclofen are discussed in relation to the physiological effects of baclofen application in vivo.