SPARKS, Garrett; BRAILOIU, Eugen; BRAILOIU, G. Cristina; DUN, Nae J.; TABOR , Jami; COOPER, Robin L.; Dept of Biol, Univ of KY; E Tenn St Univ; E Tenn St Univ; E Tenn St Univ; Sch of Med, Univ of KY; Dept of Biol, Univ of KY: Effects of m-CPP in altering neuronal function: Blocking depolarization in invertebrate motor & sensory neurons but exciting rat sensory neurons.

Although the compound m-chlorophenylpiperazine (m-CPP) is used clinically to manipulate serotonergic function, its precise mechanisms of action are not well understood. m-CPP alters synaptic transmission and neuronal function in vertebrates by non-selective agonistic actions on 5-HT₁ and 5-HT₂ receptors. In this study, we demonstrated that m-CPP is not working through a 5-HT receptor in depressing neuronal function in the invertebrates (crayfish and Drosophila), but rather likely by decreasing sodium influx through voltage-gated sodium channels present in motor and primary sensory neurons. Intracellular axonal recordings showed that m-CPP reduced the amplitude of the action potentials in crayfish motor neurons, accounting for the reduced postsynaptic potential measured in crayfish and Drosophila. Quantal analysis of excitatory postsynaptic currents, recorded at neuromuscular junctions of crayfish, indicated a reduction in the number of presynaptic vesicular events, leading to a decrease in mean quantal content. Primary sensory neurons in the crayfish exhibit decreased activity when exposed to m-CPP. In contrast, serotonin produces an increase in synaptic strength at the crayfish NMJ and increase in activity of sensory neurons while showing no effect at the Drosophila NMJ. In the rat spinal cord, the occurrence of mEPSPs is enhanced with exposure to m-CPP with no alteration in the evoked currents. Funded by NSF IBN-0131459 (RLC), NSF-REU and a G. Ribble Fellowship at the Univ of KY (JT & GMS) and a Beckman Undergraduate Research Scholarship (GMS).