Effects of microiontophoretic pentobarbitone on conditioned inhibitions mediated by GABA-A receptors in the cuneate nucleus of the rat in-vivo.

We have studied the effects of microiontophoretic sodium pentobarbitone on the conditioned inhibition of the negative potential (N-wave) evoked in the cuneate nucleus of the rat bv electrical stimulation (5 V, 0.2 ms, 0.5 Hz) of the ipsilateral forepaw. Five- or seven-barelled micropipettes were used, the tip being placed at a depth of 600-900 micron below the dorsal surface of the medulla oblongata. The conditioned inhibition was elicited by a previous identical stimulus. When the interval between the stimuli is shorter than about 40 ms (short duration) the inhibition is thought to be mediated by gamma-aminobutyric acid (GABA), acting on GABA-A receptors. When it is longer (long duration conditioned inhibition) GABA-A receptors are not thought to be involved. Microiontophoretic sodium pentobarbitone potentiated both short (15 ms) and long (45 ms) duration conditioned inhibitions. The effect was current-dependent and appeared whether or not the first N-wave was depressed. Microiontophoretic application of (-)-bicuculline methiodide (a GABA-A antagonist) reduced the potentiation by pentobarbitone up to the basal inhibition when the interval between the stimuli was 45 ms or longer and to a greater extent when it was 30 ms or shorter. It seems likely that pentobarbitone prolongs the GABA-ergic mechanism which produces the short duration inhibition, making it visible with long stimulus intervals, super-imposed upon the normal long duration conditioned inhibition which is not potentiated by local pentobarbitone.