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 hooded rats. Supramaximally activated conducting action potentials and extracellular K+ activity were recorded with microelectrodes from the cuneatus-gracilis fasciculi and corticospinal tract. In the cuneatus-gracilis fasciculi, 8-OH-DPAT (10(-4) M) significantly reduced response amplitudes 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) reduced/amplitudes by 31.7 +/- 15.0% (P < 0.0001, n = 28) and increased latencies by 6.1 +/- 5.4% (P < 0.0001). However, neither GABA nor 8-OH-DPAT significantly altered conduction velocities, suggesting that the latency shifts are due to changes in activation time and not conduction velocity. 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), increased latencies by 5.3 +/- 2.3% (P < 0.05), and did not change conduction velocities. Bicuculline or picrotoxin blocked the GABA effects but did not affect the 8-OH-DPAT effects on both tracts. The potassium channel blocker tetraethylammonium did not alter the 8-OH-DPAT effects. The Na+/K(+)-ATPase inhibitor ouabain (10(-6) M) markedly enhanced the depressive 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 suggest that GABA and serotonin agonists depress axonal excitability through different and independent mechanisms.
Sakuma
J
J
Department of Neurosurgery, New York University Medical Center, NY 10016, USA.
Ciporen
J
J
Abrahams
J
J
Young
W
W
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D001369:Axons / Q000187:drug effects*; D051381:Rats; D011930:Reaction Time / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D005680:gamma-Aminobutyric Acid; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin