alpha sub(2C)-Adrenoceptor-Overexpressing Mice Are Impaired in Executing Nonspatial and Spatial Escape Strategies

Drugs acting via alpha sub(2)-adrenoceptors modulate cognitive functions mediated via frontostriatothalamic feedback loops. The alpha sub(2C)-adrenoceptor subtype is expressed in the basal ganglia, hippocampus, and neocortex, areas that are involved in memory and other cognitive functions. alpha sub...

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Veröffentlicht in:Molecular pharmacology 1998-09, Vol.54 (3), p.569-576
Hauptverfasser: Bjoerklund, M, Sirvioe, J, Puolivaeli, J, Sallinen, J, Jaekaelae, P, Scheinin, M, Kobilka, B K, Riekkinen, P Jr
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Sprache:eng
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Zusammenfassung:Drugs acting via alpha sub(2)-adrenoceptors modulate cognitive functions mediated via frontostriatothalamic feedback loops. The alpha sub(2C)-adrenoceptor subtype is expressed in the basal ganglia, hippocampus, and neocortex, areas that are involved in memory and other cognitive functions. alpha sub(2C)-Overexpressing (OE) mice were impaired in spatial or nonspatial water maze (WM) tests, and alpha sub(2) antagonist treatment fully reversed the WM escape defect in OE mice. However, alpha sub(2C)-overexpression did not influence open field and passive avoidance behaviors or cortical EEG arousal or the actions of alpha sub(2) agonist or antagonist drugs on these functions. Our results suggest that alpha sub(2C)-adrenoceptors can modulate navigation to a hidden or visible escape platform, whereas many other actions of alpha sub(2)-adrenergic agents, such as sedation, are not mediated via alpha sub(2C)-adrenoceptors. Therefore, alpha sub(2)-agonists lacking alpha sub(2C)-AR affinity or alpha sub(2C)-AR subtype-selective alpha sub(2) antagonists could modulate functioning of frontostriatothalamic feedback loops more effectively than the current subtype-nonselective drugs.
ISSN:0026-895X