Abstract |
Survivors of exposure to an organophosphorus nerve agent may develop a number of complications including long-term cognitive deficits (Miyaki et al., 2005; Nishiwaki et al., 2001). We recently demonstrated that inhibition of the prostaglandin E2 receptor, EP2, attenuates neuroinflammation and neurodegeneration caused by status epilepticus (SE) induced by the soman analog, diisopropylfluorophosphate ( DFP), which manifest within hours to days of the initial insult. Here, we tested the hypothesis that DFP exposure leads to a loss of cognitive function in rats that is blocked by early, transient EP2 inhibition. Adult male Sprague-Dawley rats were administered vehicle or the competitive EP2 antagonist, TG6-10-1, (ip) at various times relative to DFP-induced SE. DFP administration resulted in prolonged seizure activity as demonstrated by cortical electroencephalography (EEG). A single intraperitoneal injection of TG6-10-1 or vehicle 1 h prior to DFP did not alter the development of seizures, the latency to SE or the duration of SE. Rats administered six injections of TG6-10-1 starting 90 min after the onset of DFP-induced SE could discriminate between a novel and familiar object 6-12 weeks after SE, unlike vehicle treated rats which showed no preference for the novel object. By contrast, behavioral changes in the light-dark box and open field assays were not affected by TG6-10-1. Delayed mortality after DFP was also unaffected by TG6-10-1. Thus, selective inhibition of the EP2 receptor may prevent SE-induced memory impairment in rats caused by exposure to a high dose of DFP.
|
Authors | Asheebo Rojas, Thota Ganesh, Zahra Manji, Theon O'neill, Raymond Dingledine |
Journal | Neuropharmacology
(Neuropharmacology)
Vol. 110
Issue Pt A
Pg. 419-430
(11 2016)
ISSN: 1873-7064 [Electronic] England |
PMID | 27477533
(Publication Type: Journal Article)
|
Copyright | Copyright © 2016 Elsevier Ltd. All rights reserved. |
Chemical References |
- Indoles
- Nootropic Agents
- Receptors, Prostaglandin E, EP2 Subtype
- TG6-10-1
- Isoflurophate
|
Topics |
- Animals
- Anxiety
(drug therapy, metabolism)
- Brain
(drug effects, physiopathology)
- Discrimination, Psychological
(drug effects, physiology)
- Disease Models, Animal
- Electroencephalography
- Exploratory Behavior
(drug effects, physiology)
- Indoles
(blood, pharmacokinetics, pharmacology)
- Isoflurophate
- Male
- Memory Disorders
(etiology, metabolism, prevention & control)
- Nootropic Agents
(blood, pharmacokinetics, pharmacology)
- Random Allocation
- Rats, Sprague-Dawley
- Receptors, Prostaglandin E, EP2 Subtype
(antagonists & inhibitors, metabolism)
- Recognition, Psychology
(drug effects, physiology)
- Status Epilepticus
(complications, drug therapy, metabolism, psychology)
|