Facilitation of spatial working memory performance following intra-prefrontal cortical administration of the adrenergic alpha1 agonist phenylephrine
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Hvoslef-Eide, M., Oomen, C., Fisher, B., Heath, C., Robbins, T., Saksida, L., & Bussey, T. (2015). Facilitation of spatial working memory performance following intra-prefrontal cortical administration of the adrenergic alpha1 agonist phenylephrine. Psychopharmacology, 232 4005-4016. https://doi.org/10.1007/s00213-015-4038-3
Rationale: Spatial working memory is dependent on the appropriate functioning of the prefrontal cortex (PFC). PFC activity can be modulated by noradrenaline (NA) released by afferent projections from the locus coeruleus. The coreuleo-cortical NA system could therefore be a target for cognitive enhancers of spatial working memory. Of the three classes of NA receptor potentially involved, the α2 and α1 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: To assess the effects of PFC infused α2 and α1 adrenergic receptor agonists on spatial working memory performance in the touchscreen continuous trialunique non-matching to location (cTUNL) task in rats. Methods: Young male rats were trained in the cTUNL paradigm. Cannulation of the mPFC allowed direct administration of GABA agonists for task validation, and phenylephrine and guanfacine to determine the effects of adrenergic agonists on task performance. Results: Infusion of muscimol and baclofen resulted in a delay-dependent impairment. Administration of the α2 agonist guanfacine had no effect, while infusion of the α1 agonist phenylephrine significantly improved working memory performance. Conclusions: Spatial working memory as measured in the rat cTUNL task is dependent on the mPFC. Enhancement of noradrenergic signalling enhanced performance in this paradigm, suggesting a significant role for the α1 receptor in this facilitation.
Working memory, noradrenaline, prefrontal cortex, rat, touchscreen, phenylephrine, guanfacine, muscimol, baclofen
This work was supported by the Innovative Medicine Initiative Joint Undertaking under grant agreement no. 115008 of which resources are composed of EFPIA inkind contribution and financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013). CJH was funded by Wellcome Trust grant 089703/Z/09/Z.
Wellcome Trust (089703/Z/09/Z)
Wellcome Trust (093875/Z/10/Z)
EC FP7 CP (115008)
External DOI: https://doi.org/10.1007/s00213-015-4038-3
This record's URL: https://www.repository.cam.ac.uk/handle/1810/250287
Creative Commons Attribution 4.0
Licence URL: http://creativecommons.org/licenses/by/4.0/