ArticlePsychopharmacology2005
Interaction between the antidepressant-like behavioral effects of beta adrenergic agonists and the cyclic AMP PDE inhibitor rolipram in rats.
Article in Psychopharmacology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 27 citations in OpenAlex.
- An Overview of PDE4 Inhibitors in Clinical Trials: 2010 to Early 2022.Molecules (Basel, Switzerland) · 2022Review
- Advances in novel molecular targets for antidepressants.Progress in neuro-psychopharmacology & biological psychiatry · 2021Review
- Noradrenergic Modulation of Fear Conditioning and Extinction.Frontiers in behavioral neuroscience · 2018Review
- Stress and glucocorticoids impair memory retrieval via β2-adrenergic, Gi/o-coupled suppression of cAMP signaling.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2011Article
- Type 4 phosphodiesterase plays different integrating roles in different cellular domains in pyramidal cortical neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2010Article
- Postsynaptic alpha-2 adrenergic receptors are critical for the antidepressant-like effects of desipramine on behavior.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2009Article
- Dual- and triple-acting agents for treating core and co-morbid symptoms of major depression: novel concepts, new drugs.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2009Review
- Beta2 adrenergic agonist, clenbuterol, enhances working memory performance in aging animals.Neurobiology of aging · 2008Article
- Adrenergic pharmacology and cognition: focus on the prefrontal cortex.Pharmacology & therapeutics · 2007Review
- Antidepressant-like effects of PDE4 inhibitors mediated by the high-affinity rolipram binding state (HARBS) of the phosphodiesterase-4 enzyme (PDE4) in rats.Psychopharmacology · 2006Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
rationaleType 4 phosphodiesterase (PDE4) is critical for hydrolysis of cAMP formed by stimulation of beta adrenergic receptors. However, it is not known if PDE4 is associated with beta adrenergic receptors in the mediation of antidepressant-like effects.
objectiveThe aim of the study is to determine the relationship between PDE4 and beta adrenergic receptor-mediated cAMP signaling in mediating antidepressant-like effects.
methodsThe effects of the PDE4 inhibitor rolipram, alone or combined with dobutamine or clenbuterol, selective beta-1 and beta-2 adrenergic agonists, respectively, on behavior were examined in rats under a differential reinforcement of low rate (DRL) schedule and rats trained to discriminate rolipram from vehicle. Their effects on cAMP in primary cultures of rat cerebral cortical neurons also were determined.
resultsRolipram (0.01-0.3 mg/kg), dobutamine (1-30 mg/kg), and clenbuterol (0.03-0.3 mg/kg) dose-dependently produced antidepressant-like effects on DRL behavior, decreasing response rate and increasing reinforcement rate. The effects of beta adrenergic agonists were potentiated by rolipram. Isobolographic analysis revealed that rolipram enhanced the antidepressant-like effect of dobutamine additively and that of clenbuterol synergistically. Consistently, a combination of ineffective doses of rolipram (0.03 mg/kg) and dobutamine (3 mg/kg) or clenbuterol (0.03 mg/kg) completely substituted for the rolipram discrimination stimulus. Further, incubation with an ineffective concentration of clenbuterol, but not dobutamine, in the presence of a subeffective concentration of rolipram, significantly increased cAMP in cultured cortical neurons.
conclusionsPDE4 plays an important role in regulating cAMP signaling by either beta-1 or beta-2 adrenergic receptors that mediate antidepressant-like actions; beta-2 adrenergic receptor-mediated cAMP signaling appears more responsive than beta-1 cAMP signaling to PDE4 inhibition.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.