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Comparison of the mGluR1 antagonist A-841720 in rat models of pain and cognition
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Morè, Lorenzo, Gravius, Andreas, Pietraszek, Malgorzata, Belozertseva, Irina, Malyshkin, Andrey, Shekunova, Elena, Barberi, Caroline, Schaefer, Daniela, Schmidt, Werner J. and Danysz, Wojciech (2007) Comparison of the mGluR1 antagonist A-841720 in rat models of pain and cognition. Behavioural Pharmacology , 18 (4). pp. 273-281. doi:10.1097/FBP.0b013e3281f19c18 ISSN 1473-5849.
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Abstract
In the current study we compared the potency of the selective metabotropic glutamate receptor (mGluR1) antagonist A-841720 (7-Azepan-1-yl-4-dimethylamino-7H-9-thia-1,5,7-triaza-fluoren-8-one) in rodent models of pain with its effects in models of learning and memory, to obtain information regarding the therapeutic window of this compound. A-841720 significantly reduced formalin-induced behaviours and complete Freund's adjuvant (CFA)-induced tactile allodynia, starting at doses of 1 and 10 mg/kg, respectively. At the dose of 3 mg/kg, however, A-841720 significantly reduced the percentage of spontaneous alternations in a radial-maze task. In contextual-fear conditioning, A-841720, given at the dose of 10 mg/kg before acquisition, significantly reduced freezing behaviour tested 24 h later. In the same task, repeated treatment for 5 days did not reduce the impairing effect of the challenge dose, indicating a lack of tolerance development. In a passive-avoidance task, A-841720 at 10 mg/kg administered before acquisition, significantly reduced the latency to enter the dark box on the retention test. Given that complete Freund's adjuvant is a better measure of analgesia, these results indicate that the selective mGluR1 antagonist A-841720 has analgesic potential in a dose range at which it also produces memory impairments. This diminishes its therapeutic potential for the treatment of chronic pain.
| Item Type: | Journal Article | ||||
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| Subjects: | B Philosophy. Psychology. Religion > BF Psychology Q Science > QP Physiology |
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| Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||
| Library of Congress Subject Headings (LCSH): | Glutamic acid, Memory -- Psychological aspects, Pain -- Psychological aspects, Learning -- Psychological aspects | ||||
| Journal or Publication Title: | Behavioural Pharmacology | ||||
| Publisher: | Lippincott Williams & Wilkins | ||||
| ISSN: | 1473-5849 | ||||
| Official Date: | 2007 | ||||
| Dates: |
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| Volume: | 18 | ||||
| Number: | 4 | ||||
| Page Range: | pp. 273-281 | ||||
| DOI: | 10.1097/FBP.0b013e3281f19c18 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access |
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