title: The alpha-2A-adrenoceptor agonist, guanfacine, increases regional cerebral blood flow in dorsolateral prefrontal cortex of monkeys performing a spatial working memory task.
abstract: Research indicates that norepinephrine enhances the working memory functions of the prefrontal cortex (PFC) through actions at post-synaptic, alpha-2A adrenoceptors. The current study examined the effects of the alpha-2A adrenoreceptor agonist, guanfacine (0.7 mg/kg, i.m.), compared to saline on SPECT measures of regional cerebral blood flow (rCBF) in monkeys performing a spatial working memory task. Animals were infused with the SPECT blood flow tracer, Tcm-99m ECD, through an indwelling intravenous catheter while performing the working memory task. Guanfacine treatment significantly improved cognitive performance of the working memory task, and significantly increased rCBF values in the dorsolateral PFC, the brain region most tightly associated with performance of spatial working memory tasks. In contrast, guanfacine had no significant effect on rCBF in the superior temporal cortex, an auditory association area unrelated to task performance. These data are consistent with the hypothesis that alpha-2A adrenoceptor stimulation preferentially enhances functioning of the PFC.
authors.affiliation: Department of Diagnostic Radiology, Yale Medical School, New Haven, CT 06520-8001, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Avery
authors.forename: J S
authors.initials: JS
authors.lastname: Franowicz
authors.forename: C
authors.initials: C
authors.lastname: Studholme
authors.forename: C H
authors.initials: CH
authors.lastname: van Dyck
authors.forename: A F
authors.initials: AF
authors.lastname: Arnsten
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D005260:Female; D016316:Guanfacine / Q000494:pharmacology*; D007091:Image Processing, Computer-Assisted; D008253:Macaca mulatta; D008279:Magnetic Resonance Imaging; D008568:Memory / Q000502:physiology*; D017397:Prefrontal Cortex / Q000098:blood supply* / Q000187:drug effects; D013028:Space Perception / Q000502:physiology*; D013268:Stimulation, Chemical; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D016316:Guanfacine