Rolipram, a selective c-AMP phosphodiesterase inhibitor suppresses oro-facial dyskinetic movements in rats.
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.
Sasaki
H
H
Division of Drug Dependence and Psychotropic Drug Clinical Research, National Institute of Mental Health, Ichikawa, Japan.
Hashimoto
K
K
Maeda
Y
Y
Inada
T
T
Kitao
Y
Y
Fukui
S
S
Iyo
M
M
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
D001552:Benzazepines; D011760:Pyrrolidinones; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D006220:Haloperidol; D020889:Rolipram