{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T06:06:02Z","timestamp":1768457162606,"version":"3.49.0"},"reference-count":46,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2011,8,1]],"date-time":"2011-08-01T00:00:00Z","timestamp":1312156800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2011,8,1]],"date-time":"2011-08-01T00:00:00Z","timestamp":1312156800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["jpet.aspetjournals.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pharmacology and Experimental Therapeutics"],"published-print":{"date-parts":[[2011,8]]},"DOI":"10.1124\/jpet.111.179358","type":"journal-article","created":{"date-parts":[[2011,5,14]],"date-time":"2011-05-14T00:35:26Z","timestamp":1305333326000},"page":"641-647","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":33,"title":["Effects of Repeated Treatment with Phosphodiesterase-4 Inhibitors on cAMP Signaling, Hippocampal Cell Proliferation, and Behavior in the Forced-Swim Test"],"prefix":"10.1016","volume":"338","author":[{"given":"Lan","family":"Xiao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James P.","family":"O\u2019Callaghan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James M.","family":"O\u2019Donnell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1124\/jpet.111.179358_bib1","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1126\/science.1144400","article-title":"High-speed imaging reveals neurophysiological links to behavior in an animal model of depression","volume":"317","author":"Airan","year":"2007","journal-title":"Science"},{"key":"10.1124\/jpet.111.179358_bib2","doi-asserted-by":"crossref","first-page":"1764","DOI":"10.1038\/npp.2008.234","article-title":"Enhanced sensitivity of the MRL\/MpJ mouse to the neuroplastic and behavioral effects of chronic antidepressant treatments","volume":"34","author":"Balu","year":"2009","journal-title":"Neuropsychopharmacology"},{"key":"10.1124\/jpet.111.179358_bib3","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/0006-2952(96)00053-6","article-title":"Association of the anti-inflammatory activity of phosphodiesterase 4 (PDE4) inhibitors with either inhibition of PDE4 catalytic activity or competition for [3H]rolipram binding","volume":"51","author":"Barnette","year":"1996","journal-title":"Biochem Pharmacol"},{"key":"10.1124\/jpet.111.179358_bib4","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.jneumeth.2006.03.026","article-title":"A rapid method for the quantification of mouse hippocampal neurogenesis in vivo by flow cytometry. Validation with conventional and enhanced immunohistochemical methods","volume":"157","author":"Bilsland","year":"2006","journal-title":"J Neurosci Methods"},{"key":"10.1124\/jpet.111.179358_bib5","doi-asserted-by":"crossref","first-page":"2511","DOI":"10.2174\/138161206777698855","article-title":"Improving memory: a role for phosphodiesterases","volume":"12","author":"Blokland","year":"2006","journal-title":"Curr Pharm Des"},{"key":"10.1124\/jpet.111.179358_bib6","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/nbt.1598","article-title":"Design of phosphodiesterase 4D (PDE4D) allosteric modulators for enhancing cognition with improved safety","volume":"28","author":"Burgin","year":"2010","journal-title":"Nat Biotechnol"},{"key":"10.1124\/jpet.111.179358_bib7","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.neuron.2007.04.015","article-title":"Behavioral phenotypes of Disc1 missense mutations in mice","volume":"54","author":"Clapcote","year":"2007","journal-title":"Neuron"},{"key":"10.1124\/jpet.111.179358_bib8","doi-asserted-by":"crossref","first-page":"5493","DOI":"10.1074\/jbc.R200029200","article-title":"Cyclic AMP-specific PDE4 phosphodiesterases as critical components of cAMP signaling","volume":"278","author":"Conti","year":"2003","journal-title":"J Biol Chem"},{"key":"10.1124\/jpet.111.179358_bib9","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1046\/j.1471-4159.2002.00878.x","article-title":"Regulation of cAMP-specific phosphodiesterases type 4B and 4D (PDE4) splice variants by cAMP signaling in primary cortical neurons","volume":"81","author":"D\u2019Sa","year":"2002","journal-title":"J Neurochem"},{"key":"10.1124\/jpet.111.179358_bib10","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1124\/jpet.106.109678","volume":"321","author":"David","year":"2007","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/jpet.111.179358_bib11","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.brainres.2006.04.032","article-title":"Regulation of phosphodiesterase-4 (PDE4) expression in mouse brain by repeated antidepressant treatment: comparison with rolipram","volume":"1096","author":"Dlaboga","year":"2006","journal-title":"Brain Res"},{"key":"10.1124\/jpet.111.179358_bib12","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1001\/archpsyc.1997.01830190015002","article-title":"A molecular and cellular theory of depression","volume":"54","author":"Duman","year":"1997","journal-title":"Arch Gen Psychiatry"},{"key":"10.1124\/jpet.111.179358_bib13","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1016\/S0893-133X(01)00358-X","article-title":"Regulation of adult neurogenesis by antidepressant treatment","volume":"25","author":"Duman","year":"2001","journal-title":"Neuropsychopharmacology"},{"key":"10.1124\/jpet.111.179358_bib14","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1159\/000118897","article-title":"A multicenter double-blind study of three different doses of the new cAMP-phosphodiesterase inhibitor rolipram in patients with major depressive disorder","volume":"26","author":"Fleischhacker","year":"1992","journal-title":"Neuropsychobiology"},{"key":"10.1124\/jpet.111.179358_bib15","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.brainres.2007.02.090","article-title":"Changes in NMDA receptor-induced cyclic nucleotide synthesis regulate the age-dependent increase in PDE4A expression in primary cortical cultures","volume":"1149","author":"Hajjhussein","year":"2007","journal-title":"Brain Res"},{"key":"10.1124\/jpet.111.179358_bib16","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1038\/sj.npp.1301399","article-title":"Behavioral effects of chronic fluoxetine in BALB\/cJ mice do not require adult hippocampal neurogenesis or the serotonin 1A receptor","volume":"33","author":"Holick","year":"2008","journal-title":"Neuropsychopharmacology"},{"key":"10.1124\/jpet.111.179358_bib17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/bj20021698","article-title":"PDE4 cAMP phosphodiesterases: modular enzymes that orchestrate signalling cross-talk, desensitization and compartmentalization","volume":"370","author":"Houslay","year":"2003","journal-title":"Biochem J"},{"key":"10.1124\/jpet.111.179358_bib18","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/S0026-895X(25)09391-5","article-title":"Mapping the functional domains of human recombinant phosphodiesterase 4A: structural requirements for catalytic activity and rolipram binding","volume":"50","author":"Jacobitz","year":"1996","journal-title":"Mol Pharmacol"},{"key":"10.1124\/jpet.111.179358_bib19","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/S0028-3908(97)00047-6","article-title":"Electroconvulsive shock increases the phosphorylation of cAMP response element binding protein at Ser-133 in rat hippocampus but not in cerebellum","volume":"36","author":"Jeon","year":"1997","journal-title":"Neuropharmacology"},{"key":"10.1124\/jpet.111.179358_bib20","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1523\/JNEUROSCI.5236-10.2011","article-title":"Phosphodiesterase-4D knock-out and RNA interference-mediated knock-down enhance memory and increase hippocampal neurogenesis via increased cAMP signaling","volume":"31","author":"Li","year":"2011","journal-title":"J Neurosci"},{"key":"10.1124\/jpet.111.179358_bib21","doi-asserted-by":"crossref","first-page":"2404","DOI":"10.1038\/npp.2009.66","article-title":"Antidepressant- and anxiolytic-like effects of the phosphodiesterase-4 inhibitor rolipram on behavior depend on cAMP response element binding protein-mediated neurogenesis in the hippocampus","volume":"34","author":"Li","year":"2009","journal-title":"Neuropsychopharmacology"},{"key":"10.1124\/jpet.111.179358_bib22","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1016\/j.cellsig.2005.04.003","article-title":"In resting COS1 cells a dominant negative approach shows that specific, anchored PDE4 cAMP phosphodiesterase isoforms gate the activation, by basal cAMP production, of AKAP-tethered protein kinase A type II located in the centrosomal region","volume":"17","author":"McCahill","year":"2005","journal-title":"Cell Signal"},{"key":"10.1124\/jpet.111.179358_bib23","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1126\/science.1112915","article-title":"DISC1 and PDE4B are interacting genetic factors in schizophrenia that regulate cAMP signaling","volume":"310","author":"Millar","year":"2005","journal-title":"Science"},{"key":"10.1124\/jpet.111.179358_bib24","doi-asserted-by":"crossref","first-page":"3673","DOI":"10.1523\/JNEUROSCI.22-09-03673.2002","article-title":"Regulation of neurogenesis in adult mouse hippocampus by cAMP and the cAMP response element-binding protein","volume":"22","author":"Nakagawa","year":"2002","journal-title":"J Neurosci"},{"key":"10.1124\/jpet.111.179358_bib25","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.jneumeth.2003.12.006","article-title":"Focused microwave irradiation of the brain preserves in vivo protein phosphorylation: comparison with other methods of sacrifice and analysis of multiple phosphoproteins","volume":"135","author":"O\u2019Callaghan","year":"2004","journal-title":"J Neurosci Methods"},{"key":"10.1124\/jpet.111.179358_bib26","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1016\/S0022-3565(25)10128-6","article-title":"Antidepressant-like effects of rolipram and other inhibitors of cyclic adenosine monophosphate phosphodiesterase on behavior maintained by differential reinforcement of low response rate","volume":"264","author":"O\u2019Donnell","year":"1993","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/jpet.111.179358_bib27","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.tips.2004.01.003","article-title":"Antidepressant effects of inhibitors of cAMP phosphodiesterase (PDE4)","volume":"25","author":"O\u2019Donnell","year":"2004","journal-title":"Trends Pharmacol Sci"},{"key":"10.1124\/jpet.111.179358_bib28","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1111\/j.1460-9568.2008.06349.x","article-title":"Enhanced long-term potentiation and impaired learning in phosphodiesterase 4D-knockout (PDE4D) mice","volume":"28","author":"Rutten","year":"2008","journal-title":"Eur J Neurosci"},{"key":"10.1124\/jpet.111.179358_bib29","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1021\/jm00105a045","article-title":"Calcium-independent phosphodiesterase inhibitors as putative antidepressants: [3-(bicycloalkyloxy)-4-methoxyphenyl]-2-imidazolidinones","volume":"34","author":"Saccomano","year":"1991","journal-title":"J Med Chem"},{"key":"10.1124\/jpet.111.179358_bib30","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1038\/nn1969","article-title":"Adult hippocampal neurogenesis in depression","volume":"10","author":"Sahay","year":"2007","journal-title":"Nat Neurosci"},{"key":"10.1124\/jpet.111.179358_bib31","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1126\/science.1083328","article-title":"Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants","volume":"301","author":"Santarelli","year":"2003","journal-title":"Science"},{"key":"10.1124\/jpet.111.179358_bib32","doi-asserted-by":"crossref","first-page":"983","DOI":"10.2165\/0023210-200822120-00002","article-title":"The role of phosphodiesterases in schizophrenia: therapeutic implications","volume":"22","author":"Siuciak","year":"2008","journal-title":"CNS Drugs"},{"key":"10.1124\/jpet.111.179358_bib33","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1007\/s00213-007-0727-x","article-title":"Antipsychotic profile of rolipram: efficacy in rats and reduced sensitivity in mice deficient in the phosphodiesterase-4B (PDE4B) enzyme","volume":"192","author":"Siuciak","year":"2007","journal-title":"Psychopharmacology"},{"key":"10.1124\/jpet.111.179358_bib34","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/s00213-007-1014-6","article-title":"Behavioral and neurochemical characterization of mice deficient in the phosphodiesterase-4B (PDE4B) enzyme","volume":"197","author":"Siuciak","year":"2008","journal-title":"Psychopharmacology"},{"key":"10.1124\/jpet.111.179358_bib35","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1523\/JNEUROSCI.19-02-00610.1999","article-title":"Chronic antidepressant administration increases the expression of cAMP-specific phosphodiesterase 4A and 4B isoforms","volume":"19","author":"Takahashi","year":"1999","journal-title":"J Neurosci"},{"key":"10.1124\/jpet.111.179358_bib36","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1080\/07853890701483270","article-title":"Intracellular signaling pathways pave roads to recovery for mood disorders","volume":"39","author":"Tanis","year":"2007","journal-title":"Ann Med"},{"key":"10.1124\/jpet.111.179358_bib37","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1007\/BF00174056","article-title":"Effects of forskolin and cyclic nucleotides in animal models predictive of antidepressant activity: interactions with rolipram","volume":"90","author":"Wachtel","year":"1986","journal-title":"Psychopharmacology"},{"key":"10.1124\/jpet.111.179358_bib38","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1016\/0028-3908(86)90159-0","article-title":"Rolipram, a novel antidepressant drug, reverses the hypothermia and hypokinesia of monoamine-depleted mice by an action beyond postsynaptic monoamine receptors","volume":"25","author":"Wachtel","year":"1986","journal-title":"Neuropharmacology"},{"key":"10.1124\/jpet.111.179358_bib39","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1523\/JNEUROSCI.3632-07.2008","article-title":"Chronic fluoxetine stimulates maturation and synaptic plasticity of adult-born hippocampal granule cells","volume":"28","author":"Wang","year":"2008","journal-title":"J Neurosci"},{"key":"10.1124\/jpet.111.179358_bib40","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1046\/j.1471-4159.2000.741257.x","article-title":"Effects of repeated antidepressant treatment of type 4A phosphodiesterase (PDE4A) in rat brain","volume":"74","author":"Ye","year":"2000","journal-title":"J Neurochem"},{"key":"10.1124\/jpet.111.179358_bib41","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1055\/s-2007-1017435","article-title":"Results of a phase II study of the antidepressant effect of rolipram","volume":"17","author":"Zeller","year":"1984","journal-title":"Pharmacopsychiatry"},{"key":"10.1124\/jpet.111.179358_bib42","first-page":"587","article-title":"Antidepressant-like profile and reduced sensitivity to rolipram in mice deficient in the PDE4D phosphodiesterase enzyme","volume":"27","author":"Zhang","year":"2002","journal-title":"Neuropsychopharmacology"},{"key":"10.1124\/jpet.111.179358_bib43","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1038\/sj.npp.1301537","article-title":"Anxiogenic-like behavioral phenotype of mice deficient in phosphodiesterase 4B (PDE4B)","volume":"33","author":"Zhang","year":"2007","journal-title":"Neuropsychopharmacology"},{"key":"10.1124\/jpet.111.179358_bib44","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/s00213-006-0369-4","article-title":"Antidepressant-like effects of PDE4 inhibitors mediated by the high-affinity rolipram binding state (HARBS) of the phosphodiesterase-4 enzyme (PDE4) in rats","volume":"186","author":"Zhang","year":"2006","journal-title":"Psychopharmacology"},{"key":"10.1124\/jpet.111.179358_bib45","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1124\/jpet.102.047407","article-title":"Inhibitor binding to type 4 phosphodiesterase (PDE4) assessed using [3H]piclamilast and [3H]rolipram","volume":"305","author":"Zhao","year":"2003","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/jpet.111.179358_bib46","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1124\/jpet.103.053215","article-title":"Antidepressant-induced increase in high-affinity rolipram binding sites in rat brain: dependence on noradrenergic and serotonergic function","volume":"307","author":"Zhao","year":"2003","journal-title":"J Pharmacol Exp Ther"}],"container-title":["The Journal of Pharmacology and Experimental Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022356524464975?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022356524464975?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1124\/jpet.111.179358","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T02:33:53Z","timestamp":1740018833000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0022356524464975"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,8]]},"references-count":46,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2011,8]]}},"alternative-id":["S0022356524464975"],"URL":"https:\/\/doi.org\/10.1124\/jpet.111.179358","relation":{},"ISSN":["0022-3565"],"issn-type":[{"value":"0022-3565","type":"print"}],"subject":[],"published":{"date-parts":[[2011,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Effects of Repeated Treatment with Phosphodiesterase-4 Inhibitors on cAMP Signaling, Hippocampal Cell Proliferation, and Behavior in the Forced-Swim Test","name":"articletitle","label":"Article Title"},{"value":"The Journal of Pharmacology and Experimental Therapeutics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1124\/jpet.111.179358","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2011 by The American Society for Pharmacology and Experimental Therapeutics","name":"copyright","label":"Copyright"}]}}