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Research ArticleNEUROPHARMACOLOGY

Effects of Acute and Subchronic Administration of Dexefaroxan, an α2-Adrenoceptor Antagonist, on Memory Performance in Young Adult and Aged Rodents

Philippe Chopin, Francis C. Colpaert and Marc Marien
Journal of Pharmacology and Experimental Therapeutics April 2002, 301 (1) 187-196; DOI: https://doi.org/10.1124/jpet.301.1.187
Philippe Chopin
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Francis C. Colpaert
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Marc Marien
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Abstract

The present study examined the influence of dexefaroxan, a potent and selective α2-adrenoceptor antagonist, on cognitive performance in rodents. In young adult rats, dexefaroxan reversed the deficits induced by UK 14304 [5-bromo-N-(4,5-dihydro-1-H-imidazol-2-yl)-6-quinoxalinamine], scopolamine, and diazepam in a passive avoidance task. In this test, dexefaroxan also attenuated the spontaneous forgetting induced by a 15-week training-testing interval. Moreover, dexefaroxan, given immediately after training, increased the memory performance of rats trained with a weak electric footshock in the passive avoidance test, facilitated spatial memory processes in the Morris water maze task in rats, and increased the performance of mice in an object recognition test. Thus, dexefaroxan appears to have a promnesic effect in these tests by facilitating the processes of memory retention, rather than acquisition or other noncognitive influences. The facilitatory effects of dexefaroxan in young adult rats persisted even after a 21- to 25-day constant subcutaneous infusion by using osmotic minipumps, indicating that tolerance to the promnesic effect of the drug did not occur during this prolonged treatment interval. Furthermore, in the passive avoidance and Morris water maze tests, dexefaroxan ameliorated the age-related memory deficits of 24-month-old rats to a level that was comparable to that of young adult animals, and reversed the memory deficits induced by excitotoxin lesions of the nucleus basalis magnocellularis region. Together, these findings support a potential utility of dexefaroxan in the treatment of cognitive deficits occurring in Alzheimer's disease.

Footnotes

  • Abbreviations:
    AD
    Alzheimer's disease
    LC
    locus coeruleus
    LC-NA
    locus coeruleus-noradrenergic
    NBM
    nucleus basalis magnocellularis
    UK 14304
    5-bromo-N-(4,5-dihydro-1-H-imidazol-2-yl)-6-quinoxalinamine
    • Received October 11, 2001.
    • Accepted December 12, 2001.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 301 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 301, Issue 1
1 Apr 2002
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Research ArticleNEUROPHARMACOLOGY

Effects of Acute and Subchronic Administration of Dexefaroxan, an α2-Adrenoceptor Antagonist, on Memory Performance in Young Adult and Aged Rodents

Philippe Chopin, Francis C. Colpaert and Marc Marien
Journal of Pharmacology and Experimental Therapeutics April 1, 2002, 301 (1) 187-196; DOI: https://doi.org/10.1124/jpet.301.1.187

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Research ArticleNEUROPHARMACOLOGY

Effects of Acute and Subchronic Administration of Dexefaroxan, an α2-Adrenoceptor Antagonist, on Memory Performance in Young Adult and Aged Rodents

Philippe Chopin, Francis C. Colpaert and Marc Marien
Journal of Pharmacology and Experimental Therapeutics April 1, 2002, 301 (1) 187-196; DOI: https://doi.org/10.1124/jpet.301.1.187
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