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Molecular Pharmacology

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Research ArticleArticle

α2C-Adrenoceptor-Overexpressing Mice Are Impaired in Executing Nonspatial and Spatial Escape Strategies

Markus Björklund, Jouni Sirviö, Jukka Puoliväli, Jukka Sallinen, Pekka Jäkälä, Mika Scheinin, Brian K. Kobilka and Paavo Riekkinen Jr.
Molecular Pharmacology September 1998, 54 (3) 569-576; DOI: https://doi.org/10.1124/mol.54.3.569
Markus Björklund
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Jouni Sirviö
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Jukka Puoliväli
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Jukka Sallinen
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Pekka Jäkälä
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Mika Scheinin
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Brian K. Kobilka
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Paavo Riekkinen Jr.
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Abstract

Drugs acting via α2-adrenoceptors modulate cognitive functions mediated via frontostriatothalamic feedback loops. The α2C-adrenoceptor subtype is expressed in the basal ganglia, hippocampus, and neocortex, areas that are involved in memory and other cognitive functions. α2C-Overexpressing (OE) mice were impaired in spatial or nonspatial water maze (WM) tests, and α2 antagonist treatment fully reversed the WM escape defect in OE mice. However, α2C-overexpression did not influence open field and passive avoidance behaviors or cortical EEG arousal or the actions of α2 agonist or antagonist drugs on these functions. Our results suggest that α2C-adrenoceptors can modulate navigation to a hidden or visible escape platform, whereas many other actions of α2-adrenergic agents, such as sedation, are not mediated via α2C-adrenoceptors. Therefore, α2-agonists lacking α2C-AR affinity or α2C-AR subtype-selective α2 antagonists could modulate functioning of frontostriatothalamic feedback loops more effectively than the current subtype-nonselective drugs.

Footnotes

    • Received October 13, 1997.
    • Accepted May 27, 1998.
  • Send reprint requests to: Dr. Paavo Riekkinen, Jr., Department of Neuroscience and Neurology, University of Kuopio, P.O.B. 1627, FIN-70211 Kuopio, Finland. E-mail:paavojr.riekkinen{at}uku.fi

  • This study was supported by Academy of Finland, Orion Corporation Farmos, R & D Pharmaceuticals (Turku, Finland), Research and Science Foundation of Farmos, and The Finnish Medical Foundation.

  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 54 (3)
Molecular Pharmacology
Vol. 54, Issue 3
1 Sep 1998
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Research ArticleArticle

α2C-Adrenoceptor-Overexpressing Mice Are Impaired in Executing Nonspatial and Spatial Escape Strategies

Markus Björklund, Jouni Sirviö, Jukka Puoliväli, Jukka Sallinen, Pekka Jäkälä, Mika Scheinin, Brian K. Kobilka and Paavo Riekkinen
Molecular Pharmacology September 1, 1998, 54 (3) 569-576; DOI: https://doi.org/10.1124/mol.54.3.569

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Research ArticleArticle

α2C-Adrenoceptor-Overexpressing Mice Are Impaired in Executing Nonspatial and Spatial Escape Strategies

Markus Björklund, Jouni Sirviö, Jukka Puoliväli, Jukka Sallinen, Pekka Jäkälä, Mika Scheinin, Brian K. Kobilka and Paavo Riekkinen
Molecular Pharmacology September 1, 1998, 54 (3) 569-576; DOI: https://doi.org/10.1124/mol.54.3.569
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