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Journal of Neuroscience, Vol 14, 4740-4747, Copyright © 1994 by Society for Neuroscience
Kappa opioids inhibit induction of long-term potentiation in the dentate gyrus of the guinea pig hippocampus
GW Terman, JJ Wagner and C Chavkin
Department of Pharmacology, University of Washington School of Medicine, Seattle 98195.
NMDA receptor-mediated long-term potentiation (LTP) of dentate granule cell
responses to perforant path stimulation was inhibited by the kappa 1 opioid
receptor agonist U69,593. This inhibition was reversed stereospecifically
by naloxone and blocked by the selective kappa 1 antagonist
norbinaltorphimine (NBNI). NBNI, by itself, had no effect on LTP induced by
threshold stimulation but significantly enhanced LTP from more prolonged
stimulation. This effect of NBNI suggests that endogenous opioids can
regulate LTP in the dentate gyrus. In support of this hypothesis,
stimulation of dynorphin-containing fibers also blocked LTP production in
an NBNI-sensitive manner. Finally, dynorphin- mediated inhibition of LTP
acts primarily on mechanisms of induction rather than maintenance or
expression, since dynorphin released immediately before, but not
immediately after, perforant path stimulation blocked LTP. Thus, exogenous
and endogenous kappa opioids can inhibit induction of long-term
potentiation at the perforant path- granule cell synapse and may therefore
regulate plastic changes in synaptic transmission in a brain region thought
to play an important role in processes of both learning and memory and
epileptogenesis.
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