The effect of GABA and 5-HT receptor antagonists on rat dorsal root potentials

The prolonged dorsal root potential (DRP) and its associated primary afferent depolarisation and presynaptic inhibition had been shown in previous studies to be reduced by GABAA antagonists. However we show here that picrotoxin only reduces the rat DRP to 60% of its control amplitude. We have therefore searched for antagonists to other neurotransmitters that might also contribute to the DRP. The GABAB antagonist CGP 36742 had no significant effect. Similarly, antagonists specific to the serotonin (5-HT)1A receptor (MDL73005EF) and to the 5-HT3 receptor (granisetron) had no significant effect. However, methysergide significantly reduced the DRP to 71% of its control level. Combined methysergide and picrotoxin reduced the DRP to 20% of control level. We therefore propose that both GABAA and 5-HT2 receptor mechanisms may play a role in generating the DRP.