Facilitation of spatial working memory performance following intra-prefrontal cortical administration of the adrenergic alpha1 agonist XXXX .

@entity1772 @entity6341 @entity1246 @entity73 @entity2647 @entity35 @entity1774 @entity1063
RATIONALE: Spatial working memory is dependent on the appropriate functioning of the prefrontal cortex (PFC). PFC activity can be modulated by @entity1063 (NA) released by afferent projections from the locus coeruleus. The coreuleo-cortical NA system could therefore be a target for @entity73 . Of the three classes of NA receptor potentially involved, the a2 and a1 classes seem most significant, though agents targeting these receptors have yielded mixed results. This may be partially due to the use of behavioural assays that do not translate effectively from the laboratory to the clinical setting. Use of a paradigm with improved translational potential may be essential to resolve these discrepancies. OBJECTIVES: The objective of this study was to assess the effects of PFC-infused a2 and a1 adrenergic receptor agonists on spatial working memory performance in the touchscreen continuous trial-unique non-matching to location (cTUNL) task in @entity35 . METHODS: Young male @entity35 were trained in the cTUNL paradigm. Cannulation of the mPFC allowed direct administration of @entity1246 agonists for task validation, and @entity2647 and @entity1774 to determine the effects of adrenergic agonists on task performance. RESULTS: Infusion of @entity6341 and @entity1772 resulted in a @entity73 . Administration of the a2 agonist @entity1774 had no effect, whilst infusion of the a1 agonist @entity2647 significantly improved working memory performance. CONCLUSIONS: Spatial working memory as measured in the @entity35 cTUNL task is dependent on the mPFC. Enhancement of noradrenergic signalling enhanced performance in this paradigm, suggesting a significant role for the a1 receptor in this facilitation.
