ArticlePsychopharmacology2006
Antidepressant-like effects of PDE4 inhibitors mediated by the high-affinity rolipram binding state (HARBS) of the phosphodiesterase-4 enzyme (PDE4) in rats.
Article in Psychopharmacology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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31 citing papers in PubMed, 64 citations in OpenAlex.
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- Small-molecule allosteric activators of PDE4 long form cyclic AMP phosphodiesterases.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Cyclic nucleotide phosphodiesterases: potential therapeutic targets for alcohol use disorder.Psychopharmacology · 2018Review
- Intra-nucleus accumbens shell injections of R(+)- and S(-)-baclofen bidirectionally alter binge-like ethanol, but not saccharin, intake in C57Bl/6J mice.Behavioural brain research · 2014Article
- Mice deficient in phosphodiesterase-4A display anxiogenic-like behavior.Psychopharmacology · 2014Article
- Epac and the high affinity rolipram binding conformer of PDE4 modulate neurite outgrowth and myelination using an in vitro spinal cord injury model.British journal of pharmacology · 2014Article
- Clinical and molecular genetics of the phosphodiesterases (PDEs).Endocrine reviews · 2014Review
- PDE4 as a target for cognition enhancement.Expert opinion on therapeutic targets · 2013Review
- The phosphodiesterase-4 (PDE4) inhibitor rolipram decreases ethanol seeking and consumption in alcohol-preferring Fawn-Hooded rats.Alcoholism, clinical and experimental research · 2012Article
- Evaluating the links between schizophrenia and sleep and circadian rhythm disruption.Journal of neural transmission (Vienna, Austria : 1996) · 2012Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
rationalePhosphodiesterase-4 (PDE4) has two conformation states based on rolipram binding, the high-affinity rolipram binding state (HARBS) and the low-affinity rolipram binding state (LARBS); their functions remain to be fully explained.
objectiveExperiments were carried out to determine the roles of the HARBS and LARBS in the mediation of antidepressant-like effects on behavior. MATERIALS AND
methodsTwo animal models sensitive to antidepressant drugs, the forced-swim test (FST), and the differential-reinforcement-of-low-rate (DRL) 72-s operant schedule, were used to examine the antidepressant-like effects of rolipram, CDP840, and piclamilast, PDE4 inhibitors that interact differentially with the HARBS and LARBS, and MEM1018 and MEM1091, two novel PDE4 inhibitors. Drug discrimination vs rolipram and rolipram competition binding assays also were carried out.
resultsIn the FST, rolipram and piclamilast, both at 0.1 mg/kg, produced an antidepressant-like effect, i.e., reduced immobility and increased swimming, whereas, 1 mg/kg of CDP840 or 0.5 mg/kg of MEM1018 or MEM1091 was required to produce a similar effect. Consistent with this, only rolipram and piclamilast produced antidepressant-like effects in rats under the DRL schedule of reinforcement, as evidenced by decreased response rates and increased reinforcement rates. In addition, in rats trained to discriminate rolipram from its vehicle, only rolipram and piclamilast substituted. Finally, [(3)H]rolipram and [(3)H]piclamilast binding analysis revealed that CDP840 and the two novel PDE4 inhibitors MEM1018 and MEM1091 exhibited a lower affinity for the HARBS than did rolipram.
conclusionThese results suggest that the HARBS of PDE4 is the primary conformation important for antidepressant-like effects on behavior.
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