ALPHA(2C)-ADRENOCEPTOR-OVEREXPRESSING MICE ARE IMPAIRED IN EXECUTING NONSPATIAL AND SPATIAL ESCAPE STRATEGIES

Drugs acting via alpha(2)-adrenoceptors modulate cognitive functions m ediated via frontostriatothalamic feedback leaps. The alpha(2C)-adreno ceptor subtype is expressed in the basal ganglia, hippocampus, and neo cortex, areas that are involved in memory and other cognitive function s. alpha(2C)-Overexpressing (OE) mice were impaired in spatial or nons patial water maze (WM) tests, and alpha(2) antagonist treatment fully reversed the WM escape defect in OE mice. However, alpha(2C)-overexpre ssion did not influence open field and passive avoidance behaviors or cortical EEG arousal or the actions of alpha(2) agonist or antagonist drugs on these functions. Our results suggest that alpha(2C)-adrenocep tors can modulate navigation to a hidden or visible escape platform, w hereas many other actions of alpha(2)-adrenergic agents, such as sedat ion, are not mediated via alpha(2C)-adrenoceptors. Therefore, alpha(2) -agonists lacking alpha(2C)-AR affinity or alpha(2C)-AR subtype-select ive alpha(2) antagonists could modulate functioning of frontostriatoth alamic feedback loops more effectively than the current subtype-nonsel ective drugs.