PRESYNAPTIC GABA-B RECEPTOR ACTIVATION ATTENUATES SYNAPTIC TRANSMISSION TO RAT SYMPATHETIC PREGANGLIONIC NEURONS INVITRO

Intracellular recordings were made from sympathetic preganglionic neurons (SPNs) in transverse neonate rat spinal cord slices. Superfusion of gamma-aminobutyric acid (GABA; 25-100-mu-M) or (-)-baclofen (1-30-mu-M) consistently attenuated the excitatory postsynaptic potentials (EPSPs) evoked by stimulation of dorsal rootlets or lateral funiculus, without causing a significant change of the resting membrane potential and input resistance of the SPNs or of the depolarizations induced by pressure applications of glutamate; the IC50 for baclofen was 2.5-mu-M. When superfused at a higher concentration (greater-than-or-equal-to 500-mu-M) or ejected by pressure GABA caused a bicuculline-sensitive membrane hyperpolarization. The enantimer (+)-baclofen (10-50-mu-M) and the GABA(A) agonist muscimol (1-10-mu-M) had no significant effect on the EPSPs. The GABA(B) receptor antagonist 2-hydroxy-saclofen caused a 10 fold rightward shift of the baclofen dose-response curve, whereas the GABA(A) receptor antagonist bicuculline (10-50-mu-M) was ineffective. Glycine had no significant effects on the EPSPs in the concentrations (10-100-mu-M) tested here. The results indicate that of the two putative inhibitory transmitters in the spinal cord GABA but not glycine depresses EPSPs evoked in the rat SPNs by acting on presynaptic GABA(B) receptors, the activation of which results in a reduction of excitatory transmitter release.