Effects of m-CPP in altering neuronal function: blocking depolarization in invertebrate motor and sensory neurons but exciting rat dorsal horn neurons.
The compound m-chlorophenylpiperazine (m-CPP) is used clinically to manipulate serotonergic function, though its precise mechanisms of actions are not well understood. m-CPP alters synaptic transmission and neuronal function in vertebrates by non-selective agonistic actions on 5-HT(1) and 5-HT(2) receptors. In this study, we demonstrated that m-CPP did not appear to act through a 5-HT receptor in depressing neuronal function in the invertebrates (crayfish and Drosophila). Instead, m-CPP likely decreased 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. Quantal analysis of excitatory postsynaptic currents, recorded at neuromuscular junctions (NMJ) of crayfish and Drosophila, indicated a reduction in the number of presynaptic vesicular events, which produced a decrease in mean quantal content. m-CPP also decreased activity in primary sensory neurons in the crayfish. In contrast, serotonin produces an increase in synaptic strength at the crayfish NMJ and an increase in activity of sensory neurons; it produces no effect at the Drosophila NMJ. In the rat spinal cord, m-CPP enhances the occurrence of spontaneous excitatory postsynaptic potentials with no alteration in evoked currents.
Sparks
Garrett M
GM
Department of Biology, University of Kentucky, Lexington, KY 40506-0225, USA.
Brailoiu
Eugen
E
Brailoiu
G Cristina
GC
Dun
Nae J
NJ
Tabor
Jami
J
Cooper
Robin L
RL
D000818:Animals; D003400:Astacoidea; D004330:Drosophila; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects*; D005260:Female; D008297:Male; D009469:Neuromuscular Junction / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D015222:Sodium Channels / Q000187:drug effects; D013045:Species Specificity; D013116:Spinal Cord / Q000187:drug effects
D010879:Piperazines; D017366:Serotonin Receptor Agonists; D015222:Sodium Channels; D012701:Serotonin; C015068:1-(3-chlorophenyl)piperazine