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Kappa opioids inhibit induction of long-term potentiation in the dentate gyrus of the guinea pig hippocampus

GW Terman, JJ Wagner and C Chavkin
Journal of Neuroscience 1 August 1994, 14 (8) 4740-4747; DOI: https://doi.org/10.1523/JNEUROSCI.14-08-04740.1994
GW Terman
Department of Pharmacology, University of Washington School of Medicine, Seattle 98195.
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JJ Wagner
Department of Pharmacology, University of Washington School of Medicine, Seattle 98195.
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C Chavkin
Department of Pharmacology, University of Washington School of Medicine, Seattle 98195.
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Abstract

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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The Journal of Neuroscience: 14 (8)
Journal of Neuroscience
Vol. 14, Issue 8
1 Aug 1994
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Kappa opioids inhibit induction of long-term potentiation in the dentate gyrus of the guinea pig hippocampus
GW Terman, JJ Wagner, C Chavkin
Journal of Neuroscience 1 August 1994, 14 (8) 4740-4747; DOI: 10.1523/JNEUROSCI.14-08-04740.1994

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Kappa opioids inhibit induction of long-term potentiation in the dentate gyrus of the guinea pig hippocampus
GW Terman, JJ Wagner, C Chavkin
Journal of Neuroscience 1 August 1994, 14 (8) 4740-4747; DOI: 10.1523/JNEUROSCI.14-08-04740.1994
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