Substance P and cocaine-induced suppression of EPSC are mutually occlusive

We tested the hypothesis that Substance P (SP) produces the same effects as cocaine by examining their actions on excitatory synaptic transmission in the nucleus accumbens (NAc). SP produced an irreversible depression of non-NMDA receptor mediated EPSC: EC50:0.12 uM; maximal suppression: −33.4 ± 4.8% at 1 uM. Cocaine produced a reversible depression of the EPSC: EC50 of 8.3 uM; maximal suppression: −65.7 ± 5.0% at 100 uM. Both SP (1 uM) and cocaine (30 uM) suppressed NMDA receptor mediated EPSCs: −31.7 ± 4.5% (n = 7) and −47.8 ± 4.5%, respectively. At the peak of the cocaine (30 uM)-induced suppression of the non-NMDA EPSCs (−39.1 ± 4.8%), SP (1 uM) did not produce an additional suppression (5.7 ± 2.8%). On the other hand, at the peak of SP effect (−30.3 ± 2.3%) cocaine (30 uM) produced a further suppression (−15.5 ± 3.6%). Thus, SP and cocaine produce similar effects on excitatory synaptic transmission in the NAc which occlude one another.