Postsynaptic alpha-2 Adrenergic Receptors are Critical for the Antidepressant-Like Effects of Desipramine on Behavior
by
Zhang HT, Whisler LR, Huang Y, Xiang Y, O'Donnell JM.
[1] 1Department of Behavioral Medicine and Psychiatry,
West Virginia University Health Sciences Center, Morgantown, WV, USA [2]
2Department of Physiology and Pharmacology,
West Virginia University Health Sciences Center, Morgantown, WV, USA
Neuropsychopharmacology. 2008 Oct 15.


ABSTRACT

The antidepressant desipramine inhibits the reuptake of norepinephrine (NE), leading to activation of both pre- and postsynaptic adrenergic receptors, including alpha-1, alpha-2, beta-1, and beta-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 alpha-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 mug, 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 beta-adrenergic antagonists propranolol and CGP-12177 or the alpha-1 adrenergic antagonist prazosin did not alter the antidepressant-like effect of desipramine on DRL behavior. The lack of involvement of beta-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 beta-1, beta-2, or both beta-1 and beta-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 beta-1 and beta-2 adrenergic receptors. As antagonism of presynaptic alpha-2 adrenergic receptors facilitates NE release, which potentiates the effects of desipramine, the present results suggest that postsynaptic alpha-2 adrenergic receptors play an important role in its antidepressant effects.
Options
Reboxetine
Maprotiline
Imipramine
Desipramine
SSRIs v TCAs
TCA mechanisms
Atypical depression
Desipramine/5-HT2
Retarded depression
Hippocampal remdelling
Selectivity or multiplicity?
Noradrenaline and dopamine
The hippocampus in depression
ECT, melancholia and hippocampal neogenesis
Depression, antidepressants and the hippocampus
Desipramine, antidepressants and the opioid system
Desipramine (Norpramin, Pertofrane) and mu-opioid receptors


Refs
and further reading

HOME
HedWeb
Nootropics
erythroxylum-coca.com
Future Opioids
BLTC Research
MDMA/Ecstasy
Superhapiness?
Utopian Surgery?
The Abolitionist Project
The Hedonistic Imperative
The Reproductive Revolution
Critique of Huxley's Brave New World

The Good Drug Guide
The Good Drug Guide

The Responsible Parent's Guide
To Healthy Mood Boosters For All The Family