title: Rolipram, a selective c-AMP phosphodiesterase inhibitor suppresses oro-facial dyskinetic movements in rats.
abstract: Since striatal dopamine D2 receptor supersensitivity in the etiology of tardive dyskinesia has been suggested and dopamine D2 receptors are known to inhibit adenylate cyclase activity resulting in a decrease of cyclic adenosine 3',5'-monophosphate (cAMP) levels, we hypothesized that an increase in cAMP levels ameliorates the condition. In the present study, 21-day haloperidol treatment (1.5 mg/kg I.P.) in rats resulted in an increase in striatal [3H]-spiperone (D2) binding whereas [3H] SCH23390 (D1) binding was unaltered. This haloperidol treatment also induced a significantly increase in the frequency of involuntary chewing movements and tongue protrusions, which are considered as a model of tardive dyskinesia. These dyskinetic movements were suppressed by administration of rolipram (0.5 and 1.0 mg/kg I.P.), an inhibitor of the cAMP phosphodiesterase type IV. The present results suggest that selective cAMP phosphodiesterase type IV inhibitors could be putative therapeutic drugs for tardive dyskinesia.
authors.affiliation: Division of Drug Dependence and Psychotropic Drug Clinical Research, National Institute of Mental Health, Ichikawa, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Sasaki
authors.forename: K
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Y
authors.initials: Y
authors.lastname: Maeda
authors.forename: T
authors.initials: T
authors.lastname: Inada
authors.forename: Y
authors.initials: Y
authors.lastname: Kitao
authors.forename: S
authors.initials: S
authors.lastname: Fukui
authors.forename: M
authors.initials: M
authors.lastname: Iyo
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D001552:Benzazepines / Q000378:metabolism; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy*; D006220:Haloperidol / Q000009:adverse effects; D008297:Male; D011760:Pyrrolidinones / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020889:Rolipram
chemical_list: D001552:Benzazepines; D011760:Pyrrolidinones; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D006220:Haloperidol; D020889:Rolipram