NDLI: Postsynaptic α-2 Adrenergic Receptors are Critical for the Antidepressant-Like Effects of Desipramine on Behavior

Content Provider	PubMed Central
Author	Zhang, Han-ting Whisler, Lisa R. Huang, Ying Xiang, Yang O’donnell, James M.
Copyright Year	2009
Abstract	The antidepressant desipramine inhibits the reuptake of norepinephrine (NE), leading to activation of both pre- and postsynaptic adrenergic receptors, including α-1, α-2, β-1, and β-2 subtypes. However, it is not clear which adrenergic receptors are involved in mediating its antidepressant effects. Treatment of mice with desipramine (20 mg/kg, i.p.) produced an antidepressant-like effect, as evidenced by decreased immobility in the forced-swim test; this was antagonized by pretreatment with the α-2 adrenergic antagonist idazoxan (0.1–2.5 mg/kg, i.p.). Similarly, idazoxan, administered peripherally (0.5–2.5 mg/kg, i.p.) or centrally (1–10 µg, i.c.v.), antagonized the antidepressant-like effect of desipramine in rats responding under a differential-reinforcement-of-low-rate (DRL) 72-s schedule, ie, decreased response rate and increased reinforcement rate. By contrast, pretreatment with the β-adrenergic antagonists propranolol and CGP-12177 or the α-1 adrenergic antagonist prazosin did not alter the antidepressant-like effect of desipramine on DRL behavior. The lack of involvement of β-adrenergic receptors in mediating the behavioral effects of desipramine was confirmed using knockout lines. In the forced-swim test, the desipramine-induced decrease in immobility was not altered in mice deficient in β-1, β-2, or both β-1 and β-2 adrenergic receptors. In addition, desipramine (3–30 mg/kg) produced an antidepressant-like effect on behavior under a DRL 36-s schedule in mice deficient in both β-1 and β-2 adrenergic receptors. As antagonism of presynaptic α-2 adrenergic receptors facilitates NE release, which potentiates the effects of desipramine, the present results suggest that postsynaptic α-2 adrenergic receptors play an important role in its antidepressant effects.
Related Links	http://dx.doi.org/10.1038/npp.2008.184
Ending Page	1066
Starting Page	1067
File Format	PDF
ISSN	0893133X
e-ISSN	1740634X
Journal	Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
Issue Number	4
Volume Number	34
Language	English
Publisher Date	2009-03-01
Access Restriction	Open
Subject Keyword	Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Pharmacology Psychiatry and Mental Health

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