Dermorphin-induced hyperexcitability in hippocampal CA3 and CA1 in vitro

Jones, Leslie Sargent; Grooms, Sonja Y.; Salvadori, Severo; Lazarus, Lawrence H.

doi:10.1016/0014-2999(94)90633-5

Cited by 9 publications

(4 citation statements)

References 42 publications

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“…In the hippocampus, it is clear that activation of opioid receptors such as mu (m), delta (d), and kappa (k) receptors can modulate synaptic transmission and synaptic plasticity in the dentate gyrus (Bramham et al, 1991;Lewis, 1991, 1995a,b;Terman et al, 1993Terman et al, , 1994, CA1 (Wimpey et al, 1990;Watson and Lanthorn, 1993;Jones et al, 1994), and CA3 (Derrick et al, 1992;Weisskopf et al, 1993;Caudle et al, 1994). In these systems, opioid peptides may function as neurotransmitters or modulators to regulate excitability of neurons (Moises and Walker, 1985;Bramham, 1992), which has been suggested to play a role in a process associated with learning and memory (Gallagher et al, 1983;Collier and Routtenberg, 1984).…”

Section: Introductionmentioning

confidence: 99%

Orphanin FQ inhibits synaptic transmission and long-term potentiation in rat hippocampus

et al. 1997

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It is known that opioid peptides acting on opioid receptors can modulate hippocampal synaptic functions. Although a novel member of the opioid receptor family, ORL1 receptors, that displays high‐sequence homology with classical opioid receptors is abundant in the hippocampus, little is known regarding its role in synaptic function. The present study was designed to investigate whether activation of the ORL1 receptor by its natural ligand, orphanin FQ, could modulate synaptic transmission and synaptic plasticity in the hippocampus. The actions of orphanin FQ in the CA1 and dentate gyrus were examined by field potential recordings in response to stimulation of Schaffer collaterals and perforant path, respectively. Our results showed that orphanin FQ, but not the inactive analog des‐Phe1‐orphanin FQ, reduced both the slope of the excitatory postsynaptic potentials and population spike amplitude. The inhibitory effect of orphanin FQ is dose dependent and probably involves a presynaptic mechanism, as suggested by the significantly increased paired‐pulse facilitation evoked in the presence of orphanin FQ. In addition, orphanin FQ was found to inhibit the induction of long‐term potentiation at the Schaffer collateral‐CA1 synapse. These results demonstrate that orphanin FQ can function as an inhibitory modulator regulating synaptic transmission and synaptic plasticity in the hippocampus, suggesting that activation of ORL1 receptors may play an important role in synaptic plasticity involved in learning and memory. Hippocampus 7:88–94, 1997. © 1997 Wiley‐Liss, Inc.

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Section: Introductionmentioning

confidence: 99%

Orphanin FQ inhibits synaptic transmission and long-term potentiation in rat hippocampus

et al. 1997

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“…Notably, these discharges were reduced by naltrexone, and seizures did not develop for up to 3 months in the naltrexone-treated group. While Naltrexone’s target, MOR, plays a known but incompletely understood protective role in epilepsy, this receptor subtype has also been implicated in the pro-convulsive actions of morphine 91 , 92 . Our observations provide evidence that MOR may function in the pro-convulsive capacity after TBI and that naltrexone can block this effect.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective effects of naltrexone in a mouse model of post-traumatic seizures

Rodriguez,

Sharma,

Tiarks

et al. 2024

Sci Rep

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Traumatic Brain Injury (TBI) induces neuroinflammatory response that can initiate epileptogenesis, which develops into epilepsy. Recently, we identified anti-convulsive effects of naltrexone, a mu-opioid receptor (MOR) antagonist, used to treat drug addiction. While blocking opioid receptors can reduce inflammation, it is unclear if post-TBI seizures can be prevented by blocking MORs. Here, we tested if naltrexone prevents neuroinflammation and/or seizures post-TBI. TBI was induced by a modified Marmarou Weight-Drop (WD) method on 4-week-old C57BL/6J male mice. Mice were placed in two groups: non-telemetry assessing the acute effects or in telemetry monitoring for interictal events and spontaneous seizures both following TBI and naltrexone. Molecular, histological and neuroimaging techniques were used to evaluate neuroinflammation, neurodegeneration and fiber track integrity at 8 days and 3 months post-TBI. Peripheral immune responses were assessed through serum chemokine/cytokine measurements. Our results show an increase in MOR expression, nitro-oxidative stress, mRNA expression of inflammatory cytokines, microgliosis, neurodegeneration, and white matter damage in the neocortex of TBI mice. Video-EEG revealed increased interictal events in TBI mice, with 71% mice developing post-traumatic seizures (PTS). Naltrexone treatment ameliorated neuroinflammation, neurodegeneration, reduced interictal events and prevented seizures in all TBI mice, which makes naltrexone a promising candidate against PTS, TBI-associated neuroinflammation and epileptogenesis in a WD model of TBI.

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“…Notably, these discharges were reduced by naltrexone, and epilepsy did not develop for up to 3 months in the naltrexone-treated group. While Naltrexone’s target, MOR, plays a known but incompletely understood protective role in epilepsy, this receptor subtype has also been implicated in the pro-convulsive actions of morphine (56, 57). Our observations provide evidence that MOR may function in the pro-convulsive capacity after TBI and that naltrexone can block this effect.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective Effects of Naltrexone in a Mouse Model of Post-Traumatic Epilepsy

Rodriguez,

Sharma,

Tiarks

et al. 2023

Preprint

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Traumatic Brain Injury (TBI) induces neuroinflammatory responses that can initiate epileptogenesis, which develops into epilepsy. Recently, we identified the anti-convulsive effects of naltrexone, a mu-opioid receptor (MOR) antagonist. While blocking opioid receptors can reduce inflammation, it is unclear if post-TBI epileptogenesis can be prevented by blocking MORs. Here, we tested if naltrexone prevents neuroinflammation and epileptogenesis post-TBI. TBI was induced by a modified Marmarau Weight-Drop (WD) method applied to four-week-old C57BL/6J male mice. Mice were given the pro-convulsant pentylenetetrazol (PTZ) on day two post-injury while telemetry-monitored mice received PTZ on day five. Naltrexone/vehicle treatment started two hours after PTZ. Integrated EEG-video (vEEG) recorded interictal events and spontaneous seizures for three months. Molecular, histological and neuroimaging techniques were used to evaluate neuroinflammation and neurodegeneration both acutely and chronically. Peripheral immune responses were assessed through serum chemokine/cytokine measurements. We observed increases in MOR expression, nitro-oxidative stress, mRNA expression of inflammatory cytokines, microgliosis, neurodegeneration, and white matter damage in the neocortex of TBI mice. vEEG revealed increased interictal events in TBI mice, with 71% developing epilepsy. Naltrexone ameliorated neuroinflammation and neurodegeneration, reduced interictal events and prevented epilepsy, illustrating that naltrexone is a promising drug to prevent TBI-associated neuroinflammation and epileptogenesis in post-traumatic epilepsy.

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Dermorphin-induced hyperexcitability in hippocampal CA3 and CA1 in vitro

Cited by 9 publications

References 42 publications

Orphanin FQ inhibits synaptic transmission and long-term potentiation in rat hippocampus

Orphanin FQ inhibits synaptic transmission and long-term potentiation in rat hippocampus

Neuroprotective effects of naltrexone in a mouse model of post-traumatic seizures

Neuroprotective Effects of Naltrexone in a Mouse Model of Post-Traumatic Epilepsy

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