Be. Derrick et Jl. Martinez, OPIOID RECEPTOR ACTIVATION IS ONE FACTOR UNDERLYING THE FREQUENCY-DEPENDENCE OF MESSY FIBER LTP INDUCTION, The Journal of neuroscience, 14(7), 1994, pp. 4359-4367
The contribution of high-frequency synaptic activity to the induction
of long-term potentiation (LTP) in the opioid peptide-containing messy
fiber projection was investigated in vivo in anesthetized rats. Becau
se high-frequency messy fiber activity is essential for both the relea
se of opioid peptides and the induction of messy fiber LTP, we investi
gated whether the activation of opioid receptors underlies the require
ment of sustained high-frequency messy fiber activity for LTP inductio
n. Messy fiber responses were found to have a distinct threshold for t
he number of 100 Hz pulses necessary to induce LTP, with bursts of 25-
30 pulses being the minimum for LTP induction. Application of 1 nmol o
f the mu-opioid receptor agonist DAMGO to the CA3 region potentiated m
essy fiber responses, but, unlike for messy fiber LTP, this potentiati
on could be reversed by mu-opioid receptor antagonist CTOP. Stimulatio
n of the messy fibers with either a single burst of 15 pulses at 100 H
z or application of 100 pmol of DAMGO was ineffective in potentiating
messy fiber responses. However, delivery of a 15 purse burst 10 min fo
llowing DAMGO application was effective in potentiating messy fiber re
sponses. This potentiation was not reversed by CTOP and it occluded st
imulation-induced LTP, suggesting that brief bursts delivered in the p
resence of DAMGO had induced messy fiber LTP. The release of opioid pe
ptides and the resulting activation of mu-opioid receptors is suggeste
d as one factor that underlies the requirement of sustained high-frequ
ency stimulation for the induction of messy fiber LTP. Because mu-opio
id receptor activation alone is not sufficient to induce messy fiber L
TP, brief high-frequency stimulation apparently provides additional fa
ctors that also are necessary for the induction of mossy fiber LTP.