INDEPENDENT DEPRESSIVE MECHANISMS OF GABA AND (+ -)-8-HYDROXY-DIPROPYLAMINOTETRALIN HYDROBROMIDE ON YOUNG-RAT SPINAL AXONS/

We compared the effect of GABA and the serotonin receptor agonist (+/- )-8-hydroxy-dipropylaminotetralin hydrobromide (8-OH-DPAT) on compound action potential amplitudes, latency, and conduction velocity in the spinal cord isolated from young (eight to 13-day-old) Long-Evans hoode d rats. Supramaximally activated conducting action potentials and extr acellular K+ activity were recorded with microelectrodes from the cune atus-gracilis fasciculi and corticospinal tract. In the cuneatus-graci lis fasciculi, 8-OH-DPAT (10(-4) M) significantly reduced response amp litudes by 26.1+/-10.3% (mean+/-S.D., P <0.0001, paired t-test, n=27) and increased latencies by 20.3+/-7.9% (P <0.0001). GABA (10(-4) M) re duced amplitudes by 31.7+/-15.0% (P <0.0001, n=28) and increased laten cies by 6.1+/-5.4% (P <0.0001). However, neither GABA nor 8-OH-DPAT si gnificantly altered conduction velocities, suggesting that the latency shifts are due to changes in activation time and not conduction veloc ity. In cortical spinal tract, 8-OH-DPAT (10(-4) M) depressed response amplitudes by 18.9+/-9.6% (P <0.05, n=5), increased latencies by 23.3 +/-7.2% (P <0.0001), but reduced conduction velocities by 19.9+/-10.2% . GABA (10(-4) M) reduced amplitudes by 16.4+/-7.5% (P <0.01, n=5), in creased latencies by 5.3+/-2.3% (P <0.05), and did not change conducti on velocities. Bicuculline or picrotoxin blocked the GABA effects but did not affect the 8-OH-DPAT effects on both tracts. The potassium cha nnel blocker tetraethylammonium did not alter the 8-OH-DPAT effects. T he Na+/K+-ATPase inhibitor ouabain (10(-6) M) markedly enhanced the de pressive GABA effects from 27.9+/-12.0% to 49.4+/-24.5% (P <0.01, n=9) , but had no effect on 8-OH-DPAT-mediated effects. These results sugge st that GABA and serotonin agonists depress axonal excitability throug h different and independent mechanisms. Copyright (C) 1996 IBRO.