Non-selective COX inhibitors impair memory formation and short-term but not long-term synaptic plasticity
| Autor: | Jafar Doostmohammadi, Mahyar Janahmadi, Negin Saeedi, Narges Hosseinmardi, Samira Choopani, Mahgol Darvishmolla, Soomaayeh Heysieattalab, Masoumeh Gholami |
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| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Sodium Salicylate Metabolite Long-Term Potentiation Analgesic Spatial Learning Water maze Pharmacology Hippocampus 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine In vivo Animals Cyclooxygenase Inhibitors Rats Wistar Maze Learning Sodium salicylate Spatial Memory Neuronal Plasticity Aspirin Dose-Response Relationship Drug biology Long-term potentiation General Medicine Rats 030104 developmental biology chemistry Synaptic plasticity biology.protein Cyclooxygenase 030217 neurology & neurosurgery |
| Zdroj: | Naunyn-Schmiedeberg's Archives of Pharmacology. 394:1879-1891 |
| ISSN: | 1432-1912 0028-1298 |
| DOI: | 10.1007/s00210-021-02092-4 |
| Popis: | Cyclooxygenase (COX) plays a critical role in synaptic plasticity. Therefore, long-term administration of acetylsalicylic acid (ASA) and its main metabolite, salicylate, as a COX inhibitor may impair synaptic plasticity and subsequently memory formation. Although different studies have tried to explain the effects of ASA and sodium salicylate (SS) on learning and memory, the results are contradictory and the mechanisms are not exactly known. The present study was designed to investigate the effects of long-term low-dose (equivalent to prophylactic dose) and short-term high-dose (equivalent to analgesic dose) administration of ASA and SS respectively, on spatial learning and memory and hippocampal synaptic plasticity. Animals were treated with a low dose of ASA (2 mg/ml solvated in drinking water, 6 weeks) or a high dose of SS, a metabolite of ASA, (300 mg/kg, 3 days, twice-daily, i.p). Spatial memory and synaptic plasticity were assessed by water maze performance and in vivo field potential recording from CA1, respectively. Animals treated with ASA but not SS showed a significant increase in escape latency and distance moved. Furthermore, in the probe test, animals treated with both drugs spent less time in the target quadrant zone. The paired-pulse ratio (PPR) at 20-ms inter-pulse intervals (IPI) as an index of short-term plasticity in both treated groups was significantly higher than of the control group. Interestingly, none of the administered drugs affected long-term potentiation (LTP). These data suggested that long-term inhibition of COX disrupted memory acquisition and retrieval. Interestingly, cognitive impairments happened along with short-term but not long-term synaptic plasticity disturbance. |
| Databáze: | OpenAIRE |
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