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Differential Sensitivity to Psychostimulants Across Prefrontal Cognitive Tasks: Differential Involvement of Noradrenergic α1- and α2-Receptors
Journal article   Open access   Peer reviewed

Differential Sensitivity to Psychostimulants Across Prefrontal Cognitive Tasks: Differential Involvement of Noradrenergic α1- and α2-Receptors

Craig W Berridge, Jed S Shumsky, Matt E Andrzejewski, Jill A McGaughy, Robert C Spencer, David M Devilbiss and Barry D Waterhouse
Biological psychiatry (1969), v 71(5), pp 467-473
01 Mar 2012
PMID: 21890109
url
https://doi.org/10.1016/j.biopsych.2011.07.022View
Published, Version of Record (VoR) Open

Abstract

norepinephrine ADHD methylphenidate cognition dopamine prefrontal cortex
Psychostimulants improve a variety of cognitive and behavioral processes in patients with attention-deficit/hyperactivity disorder (ADHD). Limited observations suggest a potentially different dose-sensitivity of prefrontal cortex (PFC)-dependent function (narrow inverted-U-shaped dose–response curves) versus classroom/overt behavior (broad inverted U) in children with ADHD. Recent work in rodents demonstrates that methylphenidate (MPH; Ritalin) elicits a narrow inverted-U-shaped improvement in performance in PFC-dependent tests of working memory. The current studies first tested the hypothesis that PFC-dependent tasks, in general, display narrow dose sensitivity to the beneficial actions of MPH. The effects of varying doses of MPH were examined on performance of rats in two tests of PFC-dependent cognition, sustained attention and attentional set shifting. Additionally, the effect of pretreatment with the α1-antagonist prazosin (.5 mg/kg) on MPH-induced improvement in sustained attention was examined. MPH produced a broad inverted-U-shaped facilitation of sustained attention and attentional set shifting. Prior research indicates α1-receptors impair, whereas α2-receptors improve, working memory. In contrast, attentional set shifting is improved with α1-receptor activation, whereas α2-receptors exert minimal effects in this task. Given the similar dose sensitivity of sustained attention and attentional set-shifting tasks, additional studies examined whether α1-receptors promote sustained attention, similar to attentional set shifting. In these studies, MPH-induced improvement in sustained attention was abolished by α1-receptor blockade. PFC-dependent processes display differential sensitivity to the cognition-enhancing actions of psychostimulants that are linked to the differential involvement of α1- versus α2-receptors in these processes. These observations have significant preclinical and clinical implications.

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Web of Science research areas
Neurosciences
Psychiatry
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