Mu opioid receptors are associated with the induction of hippocampal mossy fiber long-term potentiation.

We assessed the effects of antagonists selective for mu (mu), delta (delta) or kappa (kappa) opioid receptors on the induction of long-term potentiation (LTP) and short-term potentiation (STP) at the rat hippocampal mossy fiber-CA3 synapse in vivo. The mu opioid receptor-selective antagonist Cys2,Tyr3,Orn5,Pen7 amide (CTOP, 1 or 3 nmol) did not alter either mossy fiber-CA3 responses evoked at low frequencies or previously potentiated mossy fiber-CA3 responses, but it attenuated the induction of mossy fiber LTP in a dose-dependent manner. By contrast, LTP of CA3 responses evoked by stimulation of commissural afferents to the CA3 region was unaffected by CTOP. Neither the delta opioid receptor-selective antagonist naltrindole hydrochloride (0.3-10 nmol) or the kappa opioid receptor-selective antagonist nor-binaltorphimine hydrochloride (3-10 nmol) altered the induction of mossy fiber LTP. Thus, a role for delta or kappa opioid receptors in the induction of mossy fiber LTP could not be demonstrated. CTOP, in quantities that attenuated mossy fiber LTP induction, also attenuated the magnitude of mossy fiber STP measured 5 sec after delivery of conditioning trains. Further examination of the component of STP corresponding to post-tetanic potentiation (PTP) revealed that CTOP selectively attenuated the estimated magnitude and time constant of decay of mossy fiber PTP. These results suggest that the frequency-dependent activation of mu opioid receptors by endogenous opioid peptides is required for the induction of LTP at hippocampal mossy fiber synapses.(ABSTRACT TRUNCATED AT 250 WORDS)