Emetine treatment masks initial LTP without affecting long-term stability.
Applying emetine, a protein synthesis inhibitor, at 20-40μM for 90-120 min prior to LTP induction in hippocampal slices from young rats (2-3 weeks) and washing it out afterwards revealed a slowly developing potentiation that reached maximum after 20-30 min, distinct from the LTP observed under normal conditions. Nevertheless, the later phase of this potentiation was similar to standard LTP as judged by experiments lasting up to 8h after induction. Emetine preapplication for 3h without subsequent washout resulted in a substantial decay of evoked responses. By comparison between test and control pathways, LTP could still be assessed in these experiments for up to 4-6h after induction and was found not to differ from normal, except for the slow onset. The NMDA-R blocker AP5 fully blocked LTP; however, with emetine pretreatment there was an initial depression of responses with a gradual recovery during 20-30 min. This depression involved not only the field EPSP but also the presynaptic fiber volley. However, when using the protein synthesis inhibitors cycloheximide and anisomycin there was essentially no such depression. In conclusion, the present results support the idea that preexisting proteins are sufficient for inducing stable LTP. Moreover, emetine but not anisomycin or cycloheximide impairs presynaptic action potentials, leading to an apparent slow onset of LTP. The emetine-dependent effect could be due to a characteristic blocking spectrum of the drug, preferred targeting of presynaptic compartments or effects unrelated to protein synthesis.
Department of Medical Biophysics, Institute of Neuroscience and Physiology, University of Gothenburg, Sweden. abdul-karim.abbas@neuro.gu.se
Abdul-Karim
AK
Abbas
Fen-Sheng
FS
Huang
Rui
R
Li
Jörgen
J
Ekström
Holger
H
Wigström
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004640:Emetine / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects*; D017729:Presynaptic Terminals / Q000187:drug effects*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D011500:Protein Synthesis Inhibitors; D000841:Anisomycin; D003513:Cycloheximide; D004640:Emetine