OPIOID RECEPTOR ACTIVATION IS ONE FACTOR UNDERLYING THE FREQUENCY-DEPENDENCE OF MESSY FIBER LTP INDUCTION

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.