Substance P and serotonin mutually reverse their excitatory effects in the rat nucleus tractus solitarius

Actions and interactions of serotonin and substance P are described in the nucleus tractus solitarius using coronal brainstem slices and intracellular recordings. Substance P (10-100 nM) and serotonin (10-100 microM) applied alone were excitatory, causing depolarization and increasing the input resistance. Reversing effect was obtained using a protocol of long (greater than 5 min) conditioning applications of substance P and shorter (20-60 s) test applications of serotonin: serotonin, which was excitatory by itself during controls, became inhibitory for the steady action potential discharges induced by conditioning substance P applications. In the reverse situation, inhibition was also obtained using prolonged conditioning exposures to serotonin and test applications of substance P. Prolonged conditioning applications (greater than 5 min) were required in these experiments since addition or potentiation, but not inhibition, was found when combining 20-60 s substance P and serotonin applications. In addition to their excitatory effects, substance P and serotonin, applied alone, had another mechanism of action. They reduced the duration of tetraethylammonium-prolonged action potentials. This mechanism was also reversed using conditioning applications of substance P or serotonin. Thus, reversing effects appeared simultaneously on multiple ionic mechanisms. Furthermore, the reversing effect was unaffected in tetrodotoxin-treated preparations, which indicates a postsynaptic phenomenon. Consequently, the control of two different postsynaptic ionic mechanisms during substance P and serotonin interaction suggests that the underlying mechanisms take place at a common level, possibly in relation to second messenger processes. From a functional point of view, these results support the idea that in the nucleus tractus solitarius the effects of either neurotransmitter, serotonin or substance P, can be completely reversed by a previous release of the other one.