Journal
NEUROBIOLOGY OF DISEASE
Volume 23, Issue 3, Pages 679-688Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2006.05.007
Keywords
locomotor activity; coloboma mouse; attention deficit; hyperactivity disorder; norepinephrine; alpha(2C)-adrenergic receptor; beta-adrenergic receptor; dose-response; MK 912; yohimbine; clonidine
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Funding
- NINDS NIH HHS [R01 NS34845, F31 NS42489, R01 NS034845] Funding Source: Medline
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Drugs that modify noradrenergic transmission such as atomoxetine and clonidine are increasingly prescribed for the treatment of attention deficit hyperactivity disorder (ADHD). However, the therapeutic targets of these compounds are unknown. Norepinephrine is also implicated in the hyperactivity exhibited by coloboma mice. To identify the receptor subtypes that regulate the hyperactivity, coloboma mice were systematically challenged with adrenergic drugs. The beta-adrenergic receptor antagonist propranolol and the alpha(1)-adrenergic receptor antagonist prazosin each had little effect on the hyperactivity. Conversely, the alpha(2)-adrenergic receptor antagonist yohimbine reduced the activity of coloboma mice but not control mice. Subtype-selective blockade of alpha(2C)-, but not alpha(2A)- or alpha(2B)-adrenergic receptors, ameliorated hyperactivity of coloboma mice without affecting activity of control mice, suggesting that alpha(2C)-adrenergic receptors mediate the hyperactivity. Localized in the basal ganglia, alpha(2C)-adrenergic receptors are in a prime position to impact locomotor activity and are, therefore, potential targets of pharmacotherapy for ADHD. (c) 2006 Elsevier Inc. All rights reserved.
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