NDLI: Behavioral responses of dopamine beta-hydroxylase knockout mice to modafinil suggest a dual noradrenergic-dopaminergic mechanism of action.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Mitchell, Heather A. Bogenpohl, James W. Liles, L. Cameron Epstein, Michael P. Bozyczko-Coyne, Donna Williams, Michael Weinshenker, David
Description	Country affiliation: United States Author Affiliation: Mitchell HA ( Department of Human Genetics, Emory University, Atlanta, GA 30322, United States.)
Abstract	Modafinil is approved for use in the treatment of excessive daytime sleepiness. The precise mechanism of modafinil action has not been elucidated, although both dopamine (DA) and norepinephrine (NE) systems have been implicated. To explore the roles of DA and NE in the mechanism of modafinil-induced arousal, dopamine beta-hydroxylase knockout (Dbh -/-) mice were examined in behavioral paradigms of arousal (photobeam breaks and behavioral scoring of sleep latency). Dbh -/- mice completely lack NE but have hypersensitive DA signaling. It was hypothesized that Dbh -/- mice would be unresponsive to modafinil if the compound acts primarily via NE, but would be hypersensitive to modafinil if it acts primarily via DA. Dbh -/- mice had increased sensitivity to the locomotor-activating and wake-promoting effects of modafinil. Paradoxically, the alpha1-adrenergic receptor antagonist, prazosin, attenuated the effects of modafinil in control mice, but not in Dbh -/- mice. Blockade of DA receptors with flupenthixol decreased modafinil-induced locomotion and wake in both control and Dbh -/- mice. These results suggest that both NE and DA are involved in the behavioral effects of modafinil in control mice, but the requirement for NE can be bypassed by hypersensitive DA signaling.
File Format	HTM / HTML
ISSN	00913057
e-ISSN	18735177
DOI	10.1016/j.pbb.2008.07.014
Journal	Pharmacology Biochemistry and Behavior
Issue Number	2
Volume Number	91
Language	English
Publisher	Elsevier
Publisher Date	2008-12-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Behavioral Sciences Discipline Biochemistry Discipline Pharmacology Behavior, Animal Drug Effects Benzhydryl Compounds Pharmacology Central Nervous System Stimulants Dopamine Beta-hydroxylase Genetics Physiology Dopamine Norepinephrine Adrenergic Alpha-1 Receptor Antagonists Adrenergic Alpha-antagonists Animals Antagonists & Inhibitors Dopamine Antagonists Dopamine Plasma Membrane Transport Proteins Flupenthixol Mice Mice, Inbred C57bl Mice, Knockout Motor Activity Prazosin Receptors, Adrenergic Receptors, Dopamine Wakefulness Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Biological Psychiatry Behavioral Neuroscience Biochemistry Clinical Biochemistry Toxicology Pharmacology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Mice with chronic norepinephrine deficiency resemble amphetamine-sensitized animals.

Changes in EEG spectral power in the prefrontal cortex of conscious rats elicited by drugs interacting with dopaminergic and noradrenergic transmission.

Possible dopaminergic stimulation of locus coeruleus alpha1-adrenoceptors involved in behavioral activation.

Behavioral responses of dopamine β-hydroxylase knockout mice to modafinil suggest a dual noradrenergic-dopaminergic mechanism of action

The alpha1A-adrenoceptor gene is required for the alpha1L-adrenoceptor-mediated response in isolated preparations of the mouse prostate.

Effects of disulfiram and dopamine beta-hydroxylase knockout on cocaine-induced seizures.

Alpha- and beta-adrenergic stimulation of arachidonic acid metabolism in cells in culture.

Noradrenergic modulation of wakefulness/arousal.

Role of dopamine D1-like receptors in methamphetamine locomotor responses of D2 receptor knockout mice.

Behavioral responses of dopamine beta-hydroxylase knockout mice to modafinil suggest a dual noradrenergic-dopaminergic mechanism of action.

Similar Documents

Mice with chronic norepinephrine deficiency resemble amphetamine-sensitized animals.

Changes in EEG spectral power in the prefrontal cortex of conscious rats elicited by drugs interacting with dopaminergic and noradrenergic transmission.

Possible dopaminergic stimulation of locus coeruleus alpha1-adrenoceptors involved in behavioral activation.

Behavioral responses of dopamine β-hydroxylase knockout mice to modafinil suggest a dual noradrenergic-dopaminergic mechanism of action

The alpha1A-adrenoceptor gene is required for the alpha1L-adrenoceptor-mediated response in isolated preparations of the mouse prostate.

Effects of disulfiram and dopamine beta-hydroxylase knockout on cocaine-induced seizures.

Alpha- and beta-adrenergic stimulation of arachidonic acid metabolism in cells in culture.

Noradrenergic modulation of wakefulness/arousal.

Role of dopamine D1-like receptors in methamphetamine locomotor responses of D2 receptor knockout mice.

Behavioral responses of dopamine beta-hydroxylase knockout mice to modafinil suggest a dual noradrenergic-dopaminergic mechanism of action.