ACTIONS OF ENDOGENOUS OPIOIDS ON NMDA RECEPTOR-INDEPENDENT LONG-TERM POTENTIATION IN AREA CA3 OF THE HIPPOCAMPUS

The opioid peptides represent a major class of neurotransmitter in the vertebrate nervous system and are prevalent in the hippocampus. There is considerable interest in the physiological function of the opioids contained in the messy fiber pathway. The release of opioids from mes sy fibers shows a strong frequency dependence. Long-term potentiation (LTP) at this synapse, an NMDA receptor-independent form of LTP, also depends on high-frequency synaptic activity, and this has led to specu lation that endogenous opioids may be a critical factor in LTP inducti on. Previous reports using extracellular recordings have provided evid ence for and against a role for opioids in messy fiber LTP, Using sing le-cell recording techniques, we have tested the hypothesis that endog enous opioids are required for messy fiber LTP induction. We recorded from a defined population of synapses that had EPSCs with fast rise ti mes, short latencies, and monophasic decays, consistent with a proxima lly terminating synapse. The opioid antagonist naloxone prevented mess y fiber LTP in the rat, but had no effect on the commissural/associati onal system, a nonopioid-containing pathway. The action of naloxone wa s not mediated through disinhibition because GABA(A) receptors were ph armacologically blocked in these experiments. We also tested the hypot hesis that variations in postsynaptic receptor subtype distribution be tween species might explain previous controversies regarding the role of endogenous opioids. In contrast to the rat, LTP of the messy fiber field potential in guinea pig was not blocked by naloxone. Our data su ggest that opioids may be the presynaptically released, frequency-depe ndent, associative factor for messy fiber LTP induction.