title: Naltrexone prevents delayed encephalopathy in rats poisoned with the sarin analogue diisopropylflurophosphate.
abstract: BACKGROUND
  Acute poisoning with organophosphate compounds can cause chronic neuropsychological disabilities not prevented by standard antidotes of atropine and pralidoxime. We determine the efficacy of naltrexone in preventing delayed encephalopathy after poisoning with the sarin analogue diisofluorophosphate (DFP) in rats.
  
  
  METHODS
  A randomized controlled experiment was conducted. Rats were randomly assigned to receive a single intraperitoneal (IP) injection of 5 mg/kg DFP (n = 12) or vehicle control (isopropyl alcohol, n = 5). Rats were observed for cholinesterase toxicity and treated with IP atropine (2 mg/kg) and pralidoxime (25 mg/kg) as needed. After resolution of acute toxicity, rats injected with DFP were again randomized to receive daily injections of naltrexone (5 mg/kg per day) or saline (vehicle control). Control animals also received daily injections of saline. For 4 weeks after acute poisoning, rats underwent neurologic testing with the Morris Water Maze for assessment of spatial learning and reference memory. Comparisons on each test day were made across groups using analysis of variance followed by Fisher's least significant difference. Comparisons of changes in performance between first and last test day within each group were made using a paired t test. Significance was determined at P < .05.
  
  
  RESULTS
  All rats receiving DFP developed toxicity requiring rescue. Spatial learning was significantly worse in the DFP-only group compared with the naltrexone-treated and control groups at day 10 (P = .0078), day 13 (P = .01), day 24 (P = .034), and day 31 (P = .03). No significant differences in reference memory were detected at any time point.
  
  
  CONCLUSIONS
  Naltrexone protected against impairment of spatial learning from acute poisoning with DFP in rats.
authors: Department of Emergency Medicine, Brody School of Medicine at East Carolina University, Greenville, NC 27834, USA.
authors: Kori L
authors: KL
authors: Brewer
authors: Michelle M
authors: MM
authors: Troendle
authors: Laura
authors: L
authors: Pekman
authors: William J
authors: WJ
authors: Meggs
mesh_terms: D000818:Animals; D001927:Brain Diseases / Q000139:chemically induced / Q000517:prevention & control*; D002491:Central Nervous System Agents / Q000627:therapeutic use*; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D007274:Injections, Intraperitoneal; D007531:Isoflurophate / Q000008:administration & dosage / Q000009:adverse effects*; D007858:Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D009271:Naltrexone / Q000627:therapeutic use*; D020258:Neurotoxicity Syndromes / Q000209:etiology; D051381:Rats; D020318:Rats, Long-Evans; D012524:Sarin / Q000031:analogs & derivatives
chemical_list: D002491:Central Nervous System Agents; D002800:Cholinesterase Inhibitors; D007531:Isoflurophate; D009271:Naltrexone; D012524:Sarin