PROLONGED GABA(B) RECEPTOR-MEDIATED SYNAPTIC INHIBITION IN THE CAT SPINAL COLD - AN IN-VIVO STUDY

In pentobarbitone-anaesthetised spinal cats, a comparison was made of the effects of intravenous bicuculline hydrochloride, a GABA(A)-recept or antagonist, and several (-)-baclofen (GABA(B)-receptor) antagonists (CGP 35348, 46381, 56999A) on the prolonged inhibition of extensor-mu scle monosynaptic reflexes, recorded from lumbar ventral roots, by bri ef or continuous tetanic stimulation of low-threshold afferent fibres of hindlimb flexor muscles. Two components of brief tetanus inhibition were detected. Whilst possibly of similar central latency, the inhibi tion associated with GABA(B) receptors had a longer time course than t hat reduced by bicuculline. Furthermore, whereas bicuculline reduced p rimary afferent depolarization, generated by the inhibitory volleys, a nd detected as dorsal-root potentials, such potentials were general ly enhanced by intravenous baclofen antagonists. The inhibition of refle xes during and after continuous (333 Hz) tetanic flexor-nerve stimulat ion appeared to be predominantly associated with the activation of GAB A(B) receptors. In the period following continuous tetanic flexor-nerv e stimulation, during which monosynaptic extensor reflexes were reduce d in amplitude, the action potentials of the intraspinal terminations of extensor-muscle group-Ia afferent fibres were reduced in duration, as detected by the time course of the recovery of the threshold to ext racellular microstimulation following the arrival of an orthodromic im pulse. A reduction in termination action-potential duration also accom panied the reduction by microelectrophoretic (-)-baclofen of the relea se of excitatory transmitter from group-Ia terminations, both presynap tic effects being blocked by microelectrophoretic baclofen antagonists . However, the reduction of the duration of the action potential of in dividual group-Ia terminations, which followed continuous flexor-nerve stimulation, was not sensitive to the baclofen antagonist CGP 55845A, but was diminished by bicuculline methochloride. Intravenously admini stered bicuculline hydrochloride, however, had little or no effect on the inhibition of reflexes following continuous flexor-nerve stimulati on. These observations are discussed in the context of possible intras pinal pathways and pre- and postsynaptic mechanisms for GABA(A) and GA BA(B) receptor-mediated inhibition of the monosynaptic excitation of s pinal motoneurones and of the functional significance of central GABA( B) receptor-associated inhibitory processes, given the relatively mini mal effects on motor activity and behaviour produced by baclofen antag onists that penetrate the mammalian blood-brain barrier.