{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:37:58Z","timestamp":1790948278767,"version":"4.1.0"},"reference-count":59,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2012,6,4]],"date-time":"2012-06-04T00:00:00Z","timestamp":1338768000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Alcoholism Clin &amp; Exp Res"],"published-print":{"date-parts":[[2012,12]]},"abstract":"\n Background<\/jats:title>\n \n Alcohol dependence is a complex psychiatric disorder demanding development of novel pharmacotherapies. Because the cyclic adenosine monophosphate (\n cAMP<\/jats:styled-content>\n ) signaling cascade has been implicated in mediating behavioral responses to alcohol, key components in this cascade may serve as potential treatment targets. Phosphodiesterase\u20104 (\n PDE<\/jats:styled-content>\n 4), an enzyme that specifically catalyzes the hydrolysis of\n cAMP<\/jats:styled-content>\n , represents a key point in regulating intracellular\n cAMP<\/jats:styled-content>\n levels. Thus, it was of interest to determine whether\n PDE<\/jats:styled-content>\n 4 was involved in the regulation of alcohol use and abuse.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Male\n F<\/jats:styled-content>\n awn\u2010\n H<\/jats:styled-content>\n ooded (\n FH<\/jats:styled-content>\n \/\n W<\/jats:styled-content>\n jd) rats were tested for 5% (v\/v) ethanol (EtOH) and 10% (w\/v) sucrose operant oral self\u2010administration following treatment with the selective\n PDE<\/jats:styled-content>\n 4 inhibitor rolipram (0.0125, 0.025, or 0.05\u00a0mg\/kg, subcutaneous [s.c.]); rolipram at higher doses (0.05, 0.1, and 0.2\u00a0mg\/kg, s.c.) was tested to determine its impact on the intake of\n E<\/jats:styled-content>\n t\n OH<\/jats:styled-content>\n , sucrose, or water using the 2\u2010bottle choice drinking paradigm. Subsequent open\u2010field testing was performed to evaluate the influence of higher doses of rolipram on locomotor activity.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Acute administration of rolipram dose\u2010dependently reduced operant self\u2010administration of 5%\n E<\/jats:styled-content>\n t\n OH<\/jats:styled-content>\n , but had no effect on 10% sucrose responding. Time\u2010course assessment revealed significant decreases in\n E<\/jats:styled-content>\n t\n OH<\/jats:styled-content>\n consumption after rolipram (0.1, 0.2\u00a0mg\/kg) treatment in continuous\u2010 and intermittent access to\n E<\/jats:styled-content>\n t\n OH<\/jats:styled-content>\n at 5% or 10%, respectively. Moreover, chronic rolipram treatment time\u2010dependently decreased 5%\n E<\/jats:styled-content>\n t\n OH<\/jats:styled-content>\n consumption and preference during treatment days and after the termination of rolipram administration. Rolipram at the highest doses (0.1 and 0.2\u00a0mg\/kg) did decrease locomotor activity, but the effect lasted only 10 and 20\u00a0minutes, respectively, which did not likely alter long\u2010term\n E<\/jats:styled-content>\n t\n OH<\/jats:styled-content>\n drinking.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n These results suggest that\n PDE<\/jats:styled-content>\n 4 plays a role in alcohol seeking and consumption behavior. Drugs interfering with\n PDE<\/jats:styled-content>\n 4 may be a potential pharmacotherapy for alcohol dependence.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/j.1530-0277.2012.01845.x","type":"journal-article","created":{"date-parts":[[2012,6,5]],"date-time":"2012-06-05T00:45:18Z","timestamp":1338857118000},"page":"2157-2167","source":"Crossref","is-referenced-by-count":69,"title":["The Phosphodiesterase\u20104 (\n PDE<\/scp>\n 4) Inhibitor Rolipram Decreases Ethanol Seeking and Consumption in Alcohol\u2010Preferring Fawn\u2010Hooded Rats"],"prefix":"10.1111","volume":"36","author":[{"given":"Rui\u2010Ting","family":"Wen","sequence":"first","affiliation":[{"name":"National Institute on Drug Dependence Peking University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Institute on Drug Dependence Peking University Beijing 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