Evaluation of adenosine A1 receptor agonists as neuroprotective countermeasures against Soman intoxication in rats
| Autor: | Jeffrey L. Langston, Thaddeus P. Thomas, Tsung-Ming Shih, Kristy L. Meads, Todd M. Myers |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Adenosine Soman Stimulation Status epilepticus Pharmacology Toxicology Neuroprotection Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound Adenosine A1 receptor Organophosphate Poisoning 0302 clinical medicine Seizures Animals Medicine Behavior Animal Deoxyadenosines Receptor Adenosine A1 business.industry Brain Acetylcholinesterase Adenosine A1 Receptor Agonists Disease Models Animal Neuroprotective Agents 030104 developmental biology chemistry 030220 oncology & carcinogenesis CCPA Anticonvulsants medicine.symptom business Acetylcholine medicine.drug |
| Zdroj: | Toxicology and Applied Pharmacology. 416:115466 |
| ISSN: | 0041-008X |
| Popis: | Soman, an organophosphorus (OP) compound, disrupts nervous system function through inactivation of acetylcholinesterase (AChE), the enzyme that breaks down acetylcholine at synapses. Left untreated, a state of prolonged seizure activity (status epilepticus, SE) is induced, causing widespread neuronal damage and associated cognitive and behavioral impairments. Previous research demonstrated that therapeutic stimulation of A1 adenosine receptors (A1ARs) can prevent or terminate soman-induced seizure. This study examined the ability of three potent A1AR agonists to provide neuroprotection and, ultimately, prevent observable cognitive and behavioral deficits following exposure to soman. Sprague Dawley rats were challenged with a seizure-inducing dose of soman (1.2 x LD50) and treated 1 min later with one of the following A1AR agonists: (6)-Cyclopentyladenosine (CPA), 2-Chloro-N6-cyclopentyladenosine (CCPA) or N-bicyclo(2.2.1)hept-2-yl-5'-chloro-5'-deoxyadenosine (cdENBA). An active avoidance shuttle box task was used to evaluate locomotor responses to aversive stimuli at 3, 7 and 14 days post-exposure. Animals treated with CPA, CCPA or cdENBA demonstrated a higher number of avoidance responses and a faster reaction to the aversive stimulus than the soman/saline control group across all three sessions. Findings suggest that A1AR agonism is a promising neuroprotective countermeasure, capable of preventing the long-term deficits in learning and memory that are characteristic of soman intoxication. |
| Databáze: | OpenAIRE |
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