ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2009
Postsynaptic alpha-2 adrenergic receptors are critical for the antidepressant-like effects of desipramine on behavior.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 58 citations in OpenAlex.
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- Echinacoside exhibits antidepressant-like effects through AMPAR-Akt/ERK-mTOR pathway stimulation and BDNF expression in mice.Chinese medicine · 2022Article
- Corticotropin releasing factor and norepinephrine related circuitry changes in the bed nucleus of the stria terminalis in stress and alcohol and substance use disorders.Neuropharmacology · 2021Review
- Toward a Quantification of Anhedonia: Unified Matching Law and Signal Detection for Clinical Assessment and Drug Development.Perspectives on behavior science · 2021Article
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- Are Noradrenergic Transmission Reducing Drugs Antidepressants?Frontiers in behavioral neuroscience · 2021Article
- Circuit-specific hippocampal ΔFosB underlies resilience to stress-induced social avoidance.Nature communications · 2020Article
- Modulation of Monoaminergic Systems by Antidepressants in the Frontal Cortex of Rats After Chronic Mild Stress Exposure.Molecular neurobiology · 2019Article
- Role of cortical alpha-2 adrenoceptors in alcohol withdrawal-induced depression and tricyclic antidepressants.Drug and alcohol dependence · 2017Article
- Therapeutic Potential of Selectively Targeting the αFrontiers in psychiatry · 2017Review
- Biphasic Effects of α-Asarone on Immobility in the Tail Suspension Test: Evidence for the Involvement of the Noradrenergic and Serotonergic Systems in Its Antidepressant-Like Activity.Frontiers in pharmacology · 2016Article
- RGS9-2--controlled adaptations in the striatum determine the onset of action and efficacy of antidepressants in neuropathic pain states.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Association study of three single-nucleotide polymorphisms in the cyclic adenosine monophosphate response element binding 1 gene and major depressive disorder.Experimental and therapeutic medicine · 2015Article
- Lipopolysaccharide-induced depressive-like behavior is associated with α₁-adrenoceptor dependent downregulation of the membrane GluR1 subunit in the mouse medial prefrontal cortex and ventral tegmental area.The international journal of neuropsychopharmacology · 2014Article
- Changes in behavior and ultrasonic vocalizations during antidepressant treatment in the maternally separated Wistar-Kyoto rat model of depression.Metabolic brain disease · 2014Article
- LSN2424100: a novel, potent orexin-2 receptor antagonist with selectivity over orexin-1 receptors and activity in an animal model predictive of antidepressant-like efficacy.Frontiers in neuroscience · 2014Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
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 microg, 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.
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