Milstein JA, Lehmann O, Theobald DEH, Dalley JW, Robbins TW (2004) Role of noradrenergic mechanisms in sustained attention, impulse control, and effects of methylphenidate in rats: Possible relevance to ADHD. Neuroscience 2004 Abstracts 123.6. Society for Neuroscience, San Diego, CA.
Summary: There has been renewed interest in noradrenergic (NA) modulation of sustained attention and impulse control both clinically, with the approval of the SNRI atomoxetine for the treatment of attention deficit hyperactivity disorder, as well as preclinically, in the mediation of the psychomotor effects of stimulants, where blockade of α1 adrenoreceptors counteracts the locomotor stimulant effects of d-amphetamine. The current study examines the role of NA in the modulation of sustained attention and impulse control using the 5-choice serial reaction time task (5CSRT) in rats. Experiment 1 examined the systemic antagonism of methylphenidate (MP)-induced impulsivity with either prazosin, an α1 adrenoreceptor antagonist, which antagonises the locomotor activating effects of amphetamine, or propranolol, a general β-adrenoreceptor blocker. Prazosin partially attenuated the MP-mediated increase in premature responding, but also caused generalised motor slowing, increasing both correct latency as well as latency to collect food reward. Propranolol completely abolished MP-induced impulsivity. This effect was centrally rather than peripherally mediated, as nadolol, a peripheral β-blocker failed to affect MP-induced premature responding. Other experiments examined the comparative effects of selective dopaminergic or serotonergic receptor blockade. A second experiment investigated the effects of selective anti-DBH saporin-induced prefrontal NA depletion. Animals with prefrontal depletions were unimpaired on the baseline version of the 5CSRT. However, they appeared to be slightly impaired under high event rate conditions. Effects of selective prefrontal NA depletion on MP-induced behavioural changes will also be examined. Taken together, these studies provide evidence for a role of noradrenaline in impulse control and the effects of MP.
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