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The Journal of Neuroscience, July 1, 2001, 21(13):4875-4882
The  2A-Adrenergic Receptor Plays a Protective Role
in Mouse Behavioral Models of Depression and Anxiety
Nicole L.
Schramm,
Michael P.
McDonald, and
Lee E.
Limbird
Department of Pharmacology and Center for Molecular Neuroscience,
Vanderbilt University School of Medicine, Nashville, Tennessee
37232-6600
The noradrenergic system is involved in the regulation of many
physiological and psychological processes, including the modulation of
mood. The  2-adrenergic receptors (2-ARs)
modulate norepinephrine release, as well as the release of
serotonin and other neurotransmitters, and are therefore potential
targets for antidepressant and anxiolytic drug development. The current
studies were undertaken to examine the role of the 2A
subtype of 2-AR in mouse behavioral models of depression
and anxiety. We have observed that the genetic knock-out of the
2A-AR makes mice less active in a modified version of Porsolt's forced swim test and insensitive to the antidepressant effects of the tricyclic drug imipramine in this paradigm. Furthermore, 2A-AR knock-out mice appear more anxious than
wild-type C57 Bl/6 mice in the rearing and light-dark
models of anxiety after injection stress. These findings suggest that
the 2A-AR may play a protective role in some forms of
depression and anxiety and that the antidepressant effects of
imipramine may be mediated by the 2A-AR.
Key words:
antidepressant; adrenergic receptor; anxiety; forced
swim; imipramine; light-dark test
Copyright © 2001 Society for Neuroscience 0270-6474/01/21134875-08$05.00/0
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