α2C-Adrenoceptor-Overexpressing Mice Are Impaired in Executing Nonspatial and Spatial Escape Strategies
- Markus Björklund1,
- Jouni Sirviö2,
- Jukka Puoliväli1,
- Jukka Sallinen3,
- Pekka Jäkälä1,4,
- Mika Scheinin3,
- Brian K. Kobilka5 and
- Paavo Riekkinen, Jr.1,4
- 1Department of Neurology and Neuroscience, University of Kuopio, Kuopio, FIN-70211, Finland (M.B., J.P., P.J., P.R.), 2A. I. Virtanen Institute, FIN-70211 Kuopio, Finland (J. Si.),3Department of Pharmacology and Clinical Pharmacology, University of Turku, FIN-20520 Turku, Finland (J. Sa., M.S.), 4Kuopio University Hospital, FIN-70211 Kuopio, Finland (P.J., P.R.), and 5Department of Molecular and Cellular Physiology, Howard Hughes Medical Institute and Division of Cardiovascular Medicine, Stanford University, Stanford, California 94305 (R.K.K.)
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
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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
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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.
- Abbreviations:
- AR
- adrenoceptor
- ATI
- atipamezole
- CKO
- wild-type control mice for α2C-knockout mice
- DEX
- dexmedetomidine
- EEG
- electroencephalogram
- KO
- α2C-knockout
- LC
- locus ceruleus
- OE
- α2C-overexpressing
- OF
- open field
- PA
- passive avoidance
- WM
- water maze
- WT
- wild-type control mice for α2C-overexpressing mice
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- Received October 13, 1997.
- Accepted May 27, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
